lipopeptide antibiotics from Bacillus subtilis

A lot of crops are destroyed by the phytopathogens such as fungi, bacteria, and yeast leading to economic losses to the farmers. Members of theBacillusgenus are considered as the factories for the production of biologically active molecules that are potential inhibitors of growth of phytopathogens. Plant diseases constitute an emerging threat to global food security. Many of the currently available antimicrobial agents for agriculture are highly toxic and nonbiodegradable and thus cause extended environmental pollution. Moreover, an increasing number of phytopathogens have developed resistance to antimicrobial agents. The lipopeptides have been tried as potent versatile weapons to deal with a variety of phytopathogens. All the three families ofBacilluslipopeptides, namely, Surfactins, Iturins and Fengycins, have been explored for their antagonistic activities towards a wide range of phytopathogens including bacteria, fungi, and oomycetes. Iturin and Fengycin have antifungal activiti...

Gram-negative bacteria possess intrinsic resistance to glycopeptide antibiotics so these important antibacterial medications are only suitable for the treatment of Gram-positive bacterial infections. At the same time, polymyxins are peptide antibiotics, structurally related to glycopeptides, with remarkable activity against Gram-negative bacteria. With the aim of breaking the intrinsic resistance of Gram-negative bacteria against glycopeptides, a polycationic vancomycin aglycone derivative carrying an n-decanoyl side chain and five aminoethyl groups, which resembles the structure of polymyxins, was prepared. Although the compound by itself was not active against the Gram-negative bacteria tested, it synergized with teicoplanin against Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii, and it was able to potentiate vancomycin against these Gram-negative strains. Moreover, it proved to be active against vancomycin- and teicoplanin-resistant Gram-positive bacteria.

Cyclic lipopeptides (CLPs) are a promising class of natural products with antibiotic properties. CLPs are amphiphilic molecules, composed of a fatty acid tail linked to a short oligopeptide which form a macrocylic ring structure. This review presents an overview of this class of antibiotics, focusing on the current and potential therapeutic applications and placing particular emphasis on the molecular modes of action of these compounds.

Antimicrobial peptides (AMPs) are a family of tiny peptides found throughout nature that play a vital role in various organisms' innate immune systems. Antimicrobial peptides and proteins (AMPs) are a varied family of naturally occurring chemicals produced by all multicellular organisms as a first line of defense. The rising prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) diseases is the most evident cause for concern. Traditional antimicrobial drugs work by targeting certain metabolic pathways or microbiological structures to kill or hinder bacterial growth. The development of new lead structures to combat multidrug-resistant bacteria is critical, and cationic antimicrobial peptides (AMPs) have the ability to do so. Based on the SPOT synthesis, we present an outline of a strategy for screening peptides for antimicrobial activity. Multidrug-resistant bacteria have grown fast in recent decades, leading to a rise in nosocomial infections and in-hospita...

A lot of crops are destroyed by the phytopathogens such as fungi, bacteria, and yeast leading to economic losses to the farmers. Members of theBacillusgenus are considered as the factories for the production of biologically active molecules that are potential inhibitors of growth of phytopathogens. Plant diseases constitute an emerging threat to global food security. Many of the currently available antimicrobial agents for agriculture are highly toxic and nonbiodegradable and thus cause extended environmental pollution. Moreover, an increasing number of phytopathogens have developed resistance to antimicrobial agents. The lipopeptides have been tried as potent versatile weapons to deal with a variety of phytopathogens. All the three families ofBacilluslipopeptides, namely, Surfactins, Iturins and Fengycins, have been explored for their antagonistic activities towards a wide range of phytopathogens including bacteria, fungi, and oomycetes. Iturin and Fengycin have antifungal activiti...

Polymyxin B and colistin are currently used as a 'last-line' treatment for multidrug-resistant Gram-negative bacteria. However very little is known about the pharmacological differences between polymyxin B 1 , polymyxin B 2 , colistin A, colistin B, the major cyclic lipopeptides components present in polymyxin B and colistin products. Here, we report on the in vitro and in vivo antimicrobial activity and toxicity of these major lipopeptide components. All four lipopeptides had comparable MICs (<0.125-4 mg/L) against a panel of clinical Gram-negative isolates. They also had comparable in vivo antimicrobial activity (Δlog 10 CFU/mL >-3) and nephrotoxicity (mild to moderate histological damage) in mouse models. However, polymyxin B 1 and colistin A showed significantly higher (> 3-fold) in vitro apoptotic effect on human kidney proximal tubular HK-2 cells than polymyxin B2 and colistin B, respectively. Compared to the commercial polymyxin and colistin products, the individual lipopeptide components had slightly more in vivo antimicrobial activity. Our results highlight the need to reassess pharmacopoeial standards for polymyxins B and colistin and to standardize the composition of the different commercial products of polymyxin antibiotics.

Naturally occurring cyclic depsipeptides, microbial secondary metabolites that contain one or more ester bonds in addition to the amide bonds, have emerged as an important source of pharmacologically active compounds or promising lead structures for the development of novel synthetically derived drugs. In particular, their lipidated derivatives have shown the greatest therapeutic potential as antimicrobial agents. Some of those compounds are either already marketed (daptomycin 37) or in advanced stages of clinical development (ramoplanin 32) for the treatment of complicated infections caused by multidrug-resistant bacterial strains. As bacteria progressively become resistant to frontline antimicrobial agents, our capacity to effectively treat bacterial infections becomes severely hindered. Therefore, identifying novel antibacterial targets and new antibacterial chemotherapeutics capable of treating infections from drug-resistant microorganisms is of vital importance.

A lot of crops are destroyed by the phytopathogens such as fungi, bacteria, and yeast leading to economic losses to the farmers. Members of theBacillusgenus are considered as the factories for the production of biologically active molecules that are potential inhibitors of growth of phytopathogens. Plant diseases constitute an emerging threat to global food security. Many of the currently available antimicrobial agents for agriculture are highly toxic and nonbiodegradable and thus cause extended environmental pollution. Moreover, an increasing number of phytopathogens have developed resistance to antimicrobial agents. The lipopeptides have been tried as potent versatile weapons to deal with a variety of phytopathogens. All the three families ofBacilluslipopeptides, namely, Surfactins, Iturins and Fengycins, have been explored for their antagonistic activities towards a wide range of phytopathogens including bacteria, fungi, and oomycetes. Iturin and Fengycin have antifungal activiti...

Macrocyclic peptide-based natural products have provided powerful new antibiotic drugs, drug candidates, and scaffolds for medicinal chemists as a source of inspiration to design novel antibiotics. While most of those natural products are active mainly against Gram-positive pathogens, novel macrocyclic peptide-based compounds have recently been described, which exhibit potent and specific activity against some of the most problematic Gramnegative ESKAPE pathogens. This mini-review gives an update on recent developments.

Antimicrobial peptides (AMPs) are a family of tiny peptides found throughout nature that play a vital role in various organisms&#39; innate immune systems. Antimicrobial peptides and proteins (AMPs) are a varied family of naturally occurring chemicals produced by all multicellular organisms as a first line of defense. The rising prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) diseases is the most evident cause for concern. Traditional antimicrobial drugs work by targeting certain metabolic pathways or microbiological structures to kill or hinder bacterial growth. The development of new lead structures to combat multidrug-resistant bacteria is critical, and cationic antimicrobial peptides (AMPs) have the ability to do so. Based on the SPOT synthesis, we present an outline of a strategy for screening peptides for antimicrobial activity. Multidrug-resistant bacteria have grown fast in recent decades, leading to a rise in nosocomial infections and in-hospita...

Herein, a bactericide-secreting Bacillus strain, potentially useful as a biocontrol agent, was isolated from the commercial Yanjing Natto food. Following the biochemical and physiological evaluation, the molecular identification was performed using 16S rDNA sequencing of polymerase chain reaction-amplified DNA that confirmed the natto isolate as Bacillus subtilis natto (B. subtilis natto). The biocontrol (microbial inhibitory) capability of B. subtilis natto was investigated against Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and yeast (Yarrowia lipolytica) and recorded. The antimicrobial activity of B. subtilis natto was further enhanced by optimizing the growth medium for optimal bactericides secretion. Under optimized conditions, B. subtilis natto exhibited much higher inhibitory activity against S. aureus with a zone of inhibition diameter up to 27 mm. After 48 h incubation, the optimally yielded B. subtilis natto broth was used to extract and purify the res...

Microbiologically produced surface acting compounds (biosurfactants) have very interesting properties with many potential industrial applications. Lipopeptides is a particularly promising group of biosurfactants in respect to the potentially huge number of various chemical structures. The chemical diversity results from fatty acid moiety (e.g. length, saturation, branching or hydroxylation) and type and sequence of the amino acids in the peptide chain. The limiting factor for the design and analysis of various lipopeptides is the ability of the targeted biosynthesis. Biosynthesis of particular lipopeptides may be potentially achieved by strain selection, culture conditions, or molecular engineering. The wellknown lipopeptedes (surfactins, iturins, and fengycins) producer is B. subtilis. The aim of this study was to study targeted surfactin structural analogues biosynthesis in response to culture conditions in view of the design and production of tailor-made lipopeptides. Two B. subtilis strains (KB1 and #309) were tested for surfactin production. Both strains produced a mixture of five major surfactin analogues with the number of carbons in an alkyl chain ranging from 12 to 16. The two strains differed with respect to their oxygen demand for optimal surfactin biosynthesis (lower oxygen demand for KB1). The amount of air influenced the relative ratios of surfactin analogues. Lower oxygen amount decreased the share of C15 analogues while it increased the share of C12 analogues. Thus, the biosynthesis of a desired surfactin analogue may controlled by both strain and culture conditions.

A lot of crops are destroyed by the phytopathogens such as fungi, bacteria, and yeast leading to economic losses to the farmers. Members of theBacillusgenus are considered as the factories for the production of biologically active molecules that are potential inhibitors of growth of phytopathogens. Plant diseases constitute an emerging threat to global food security. Many of the currently available antimicrobial agents for agriculture are highly toxic and nonbiodegradable and thus cause extended environmental pollution. Moreover, an increasing number of phytopathogens have developed resistance to antimicrobial agents. The lipopeptides have been tried as potent versatile weapons to deal with a variety of phytopathogens. All the three families ofBacilluslipopeptides, namely, Surfactins, Iturins and Fengycins, have been explored for their antagonistic activities towards a wide range of phytopathogens including bacteria, fungi, and oomycetes. Iturin and Fengycin have antifungal activiti...

Antibiotic resistance is a major public health challenge, and Gram-negative multidrug-resistant bacteria are particularly dangerous. The threat of running out of active molecules is accelerated by the extensive use of antibiotics in the context of the COVID-19 pandemic, and new antibiotics are urgently needed. Colistin and polymyxin B are natural antibiotics considered as last resort drugs for multi-resistant infections, but their use is limited because of neuro- and nephrotoxicity. We previously reported a series of synthetic analogues inspired in natural polymyxins with a flexible scaffold that allows multiple modifications to improve activity and reduce toxicity. In this work, we focus on modifications in the hydrophobic domains, describing analogues that broaden or narrow the spectrum of activity including both Gram-positive and Gram-negative bacteria, with MICs in the low µM range and low hemolytic activity. Using biophysical methods, we explore the interaction of the new molec...

Antibiotic resistance is a major public health challenge, and Gram-negative multidrug-resistant bacteria are particularly dangerous. The threat of running out of active molecules is accelerated by the extensive use of antibiotics in the context of the COVID-19 pandemic, and new antibiotics are urgently needed. Colistin and polymyxin B are natural antibiotics considered as last resort drugs for multi-resistant infections, but their use is limited because of neuro- and nephrotoxicity. We previously reported a series of synthetic analogues inspired in natural polymyxins with a flexible scaffold that allows multiple modifications to improve activity and reduce toxicity. In this work, we focus on modifications in the hydrophobic domains, describing analogues that broaden or narrow the spectrum of activity including both Gram-positive and Gram-negative bacteria, with MICs in the low µM range and low hemolytic activity. Using biophysical methods, we explore the interaction of the new molec...

Antimicrobial peptides (AMPs) are a family of tiny peptides found throughout nature that play a vital role in various organisms&#39; innate immune systems. Antimicrobial peptides and proteins (AMPs) are a varied family of naturally occurring chemicals produced by all multicellular organisms as a first line of defense. The rising prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) diseases is the most evident cause for concern. Traditional antimicrobial drugs work by targeting certain metabolic pathways or microbiological structures to kill or hinder bacterial growth. The development of new lead structures to combat multidrug-resistant bacteria is critical, and cationic antimicrobial peptides (AMPs) have the ability to do so. Based on the SPOT synthesis, we present an outline of a strategy for screening peptides for antimicrobial activity. Multidrug-resistant bacteria have grown fast in recent decades, leading to a rise in nosocomial infections and in-hospita...

Bacterial metabolites have been immensely useful as antibiotics, hence most of the work on the subject revolved around understanding their antibiotic properties. However, it emerged from current literature that they are pleotropic in nature as they express a broad array of activities with potential therapeutic significance. These characteristics include, but are not limited to anticancer, antiviral, antitrypanosomal, antidiabetic adjuvants, anti-inflammatory, hepatoprotective etc. A structural classification of the bacterial metabolites has been given based on the structures re-drawn from the published data. Role of the structural motifs, thought to be primarily present in fungal and plant (eukaryotic) metabolites but now reported in bacterial metabolites as well, have been discussed in light of their multifaceted activities. An analysis of the current literature pertaining to diverse therapeutic properties of the bacterial metabolites is presented.

Two novel Algerian field-collected isolates were selected for their antifungal activity against Zymoseptoria tritici (teleomorph Mycosphaerella graminicola). The novel strains, termed Alg.24B1 and Alg.24B2, were identified as Bacillus subtilis and Bacillus simplex since their respective nucleotide sequences of the 16S rRNA gene were 100% and 99.93% identical to those of B. subtilis and B. simplex, respectively. The antifungal activities of Alg.24B1 and Alg.24B2 were evaluated by the well diffusion method and compared to those of other Bacillus species. The maximum activity was obtained after two days of confrontation of the bacterial strain supernatants with the fungus for Alg.24B1 and three days for Alg.24B2. Furthermore, the metabolites responsible for the antifungal activity of both strains were detected by the investigation of either gene presence (PCR) or molecule production (activity detection of lytic enzymes and HPLC detection of lipopeptides). Overall, this study showed tha...

Two novel Algerian field-collected isolates were selected for their antifungal activity against Zymoseptoria tritici (teleomorph Mycosphaerella graminicola). The novel strains, termed Alg.24B1 and Alg.24B2, were identified as Bacillus subtilis and Bacillus simplex since their respective nucleotide sequences of the 16S rRNA gene were 100% and 99.93% identical to those of B. subtilis and B. simplex, respectively. The antifungal activities of Alg.24B1 and Alg.24B2 were evaluated by the well diffusion method and compared to those of other Bacillus species. The maximum activity was obtained after two days of confrontation of the bacterial strain supernatants with the fungus for Alg.24B1 and three days for Alg.24B2. Furthermore, the metabolites responsible for the antifungal activity of both strains were detected by the investigation of either gene presence (PCR) or molecule production (activity detection of lytic enzymes and HPLC detection of lipopeptides). Overall, this study showed tha...

A two-step ultrafiltration and liquid chromatography-electronic spray ionization-tandem mass spectrometry (LC-ESI-MS/MS) were applied to investigate the nature of lipopeptides in the methanol extract harvested from marine Bacillus megaterium. The structure of lipopeptide homologs were characterized by using collision-induced dissociation mass spectrometry analysis. Collectively, two kinds of linear fengycin A and B with a double bond were characterized for the first time besides the popular cyclic fengycin A and B with the difference in the amino acid at position 6 of the peptide moiety. It is worth noting that two kinds of linear isoforms of surfactins and two kinds of cyclic isoforms of esperin with a smaller peptide ring formed by the fifth l-Asp and β-hydroxy fatty acid were also separated and identified in addition to the all seven kinds of cyclic isoforms of surfactins. Only one analogue (bacillomycin D) of iturin family was identified in this research. To our best knowledge, this is the first report that more than 40 variants of lipopeptides from one strain of Bacillus were identified using our potent purification and identification methods.

The rapid onset of resistance reduces the efficacy of most conventional antimicrobial drugs and is a general cause of concern for human well-being. Thus, there is a great demand for a continuous supply of novel antibiotics to combat this problem. Bacteria-derived antimicrobial peptides (AMPs) have long been used as food preservatives. Thus, antimicrobial agents are predominantly significant in limiting infectious diseases. Meanwhile, the development and dissemination of drug-resistant strains in pathogenic bacteria have begun to be a significant general health threat. Therefore, the lowest effectiveness of the present antibiotics in the direction of the administration was becoming prominent to the consequence of the discussion of new antibiotics. These considerations, Bacillus sp completely famous for making different metabolites of the possibility their utilization, thus, it is completed a search to isolate Bacillus sp for the action making of anti-microorganisms compounds. The Bio...

Antimicrobial resistance is a major public health and development concern on a global scale. The increasing resistance of the pathogenic bacteria Neisseria gonorrhoeae to antibiotics necessitates efforts to identify potential alternative antibiotics from nature, including insects, which are already recognized as a source of natural antibiotics by the scientific community. This study aimed to determine the potential of components of gut-associated bacteria isolated from Apis dorsata, an Asian giant honeybee, as an antibacterial against N. gonorrhoeae by in vitro and in silico methods as an initial process in the stage of new drug discovery. The identified gut-associated bacteria of A. dorsata included Acinetobacter indicus and Bacillus cereus with 100% identity to referenced bacteria from GenBank. Cell-free culture supernatants (CFCS) of B. cereus had a very strong antibacterial activity against N. gonorrhoeae in an in vitro antibacterial testing. Meanwhile, molecular docking reveale...

The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authority of the rapporteur Member State, France, for the pesticide active substance Bacillus amyloliquefaciens strain IT‐45 and the considerations as regards the inclusion of the substance in Annex IV of Regulation (EC) No 396/2005 are reported. The context of the peer review was that required by Regulation (EC) No 1107/2009 of the European Parliament and of the Council. The conclusions were reached on the basis of the evaluation of the representative use of Bacillus amyloliquefaciens strain IT‐45 as a fungicide on citrus (field use, application to soil via drip irrigation systems). The reliable endpoints, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Multidrug-resistant (MDR) superbugs, including Acinetobacter baumannii and methicillinresistant Staphylococcus aureus (MRSA), are a challenge for healthcare professionals. In this study, the synergistic activity of vitamins with antibiotics against resistant bacterial strains was evaluated. Methods: Synergistic effects between antibiotics and stock solutions of vitamins were evaluated by the Kirby Bauer disk diffusion assay. Distilled water and propylene glycol were used as solvent for watersoluble and fat-soluble vitamins, respectively. Final concentrations of 10 mg/mL for each water-soluble vitamin [B1 (thiamine), B2 (ribo avin), fl B6 (pyridoxine), B12 (methylcobalamin) and C (ascorbic acid)] and 0.1 mg/mL for each fat-soluble vitamin [A (retinol), D (cholecalciferol), E (a-tocopherol) and K (menadione)] were used in combination with the antibiotics. Results: The results demonstrated that vitamins K and E had good synergistic activity with piperacillin/ tazobactam, imipenem and doripenem against A. baumannii, whilst vitamins B1, B2 and B12 showed remarkable synergistic activity with linezolidagainst MRSA. VitaminB1 was further shown to have better synergism with oxacillin, tetracycline, rifampicin and linezolid against MRSA. The fat-soluble vitamins E and K showedgood synergism againstGram-negative A. baumannii, whilst the water-soluble vitamins B1, B2 and B12 were effective against MRSA but not against A. baumannii. Conclusions: This synergistic action of vitamins with antibiotics may be used as a tool to treat MDR superbugs, with further evaluation required at a molecular level.

Objectives: Multidrug-resistant (MDR) superbugs, including Acinetobacter baumannii and methicillinresistant Staphylococcus aureus (MRSA), are a challenge for healthcare professionals. In this study, the synergistic activity of vitamins with antibiotics against resistant bacterial strains was evaluated. Methods: Synergistic effects between antibiotics and stock solutions of vitamins were evaluated by the Kirby Bauer disk diffusion assay. Distilled water and propylene glycol were used as solvent for watersoluble and fat-soluble vitamins, respectively. Final concentrations of 10 mg/mL for each water-soluble vitamin [B1 (thiamine), B2 (ribo avin), fl B6 (pyridoxine), B12 (methylcobalamin) and C (ascorbic acid)] and 0.1 mg/mL for each fat-soluble vitamin [A (retinol), D (cholecalciferol), E (a-tocopherol) and K (menadione)] were used in combination with the antibiotics. Results: The results demonstrated that vitamins K and E had good synergistic activity with piperacillin/ tazobactam, imipenem and doripenem against A. baumannii, whilst vitamins B1, B2 and B12 showed remarkable synergistic activity with linezolidagainst MRSA. VitaminB1 was further shown to have better synergism with oxacillin, tetracycline, rifampicin and linezolid against MRSA. The fat-soluble vitamins E and K showedgood synergism againstGram-negative A. baumannii, whilst the water-soluble vitamins B1, B2 and B12 were effective against MRSA but not against A. baumannii. Conclusions: This synergistic action of vitamins with antibiotics may be used as a tool to treat MDR superbugs, with further evaluation required at a molecular level.

Objectives: Multidrug-resistant (MDR) superbugs, including Acinetobacter baumannii and methicillinresistant Staphylococcus aureus (MRSA), are a challenge for healthcare professionals. In this study, the synergistic activity of vitamins with antibiotics against resistant bacterial strains was evaluated. Methods: Synergistic effects between antibiotics and stock solutions of vitamins were evaluated by the Kirby Bauer disk diffusion assay. Distilled water and propylene glycol were used as solvent for watersoluble and fat-soluble vitamins, respectively. Final concentrations of 10 mg/mL for each water-soluble vitamin [B1 (thiamine), B2 (ribo avin), fl B6 (pyridoxine), B12 (methylcobalamin) and C (ascorbic acid)] and 0.1 mg/mL for each fat-soluble vitamin [A (retinol), D (cholecalciferol), E (a-tocopherol) and K (menadione)] were used in combination with the antibiotics. Results: The results demonstrated that vitamins K and E had good synergistic activity with piperacillin/ tazobactam, imipenem and doripenem against A. baumannii, whilst vitamins B1, B2 and B12 showed remarkable synergistic activity with linezolidagainst MRSA. VitaminB1 was further shown to have better synergism with oxacillin, tetracycline, rifampicin and linezolid against MRSA. The fat-soluble vitamins E and K showedgood synergism againstGram-negative A. baumannii, whilst the water-soluble vitamins B1, B2 and B12 were effective against MRSA but not against A. baumannii. Conclusions: This synergistic action of vitamins with antibiotics may be used as a tool to treat MDR superbugs, with further evaluation required at a molecular level.

Lipopeptides show great potential for biomedical application. Several lipopeptides exhibit narrow and broad-spectrum inhibition activities. e aim of the study is to characterize the lipopeptides produced by B. amyloliquefaciens strain MD4-12 and evaluate the synergistic antimicrobial activity in combination with a conventional antibiotic against Gram-negative bacteria. B. amyloliquefaciens strain MD4-12 was isolated from oil-contaminated soil. e isolate was cultivated in McKeen medium, and the lipopeptides were isolated by precipitation and extraction with methanol. Characterization of the lipopeptides by ESI-MS gave nine mass ion peaks with m/z 994-1072, resulted from protonating of the main ions in [M + H] + and [M + Na] + ion form. ese mass ion peaks attributed to surfactin homologs. By tandem mass spectrometry, five variants of surfactin with the same amino acid sequence in peptide moiety could be revealed. e peptide moiety contains seven amino acids identified as Glu-Leu/Ile-Leu-Val-Asp-Leu-Leu/Ile while the fatty acid moiety comprises a different length of chain from C 12 to C 16. Surfactin showed antibacterial activity against various Gram-positive and Gram-negative bacteria. Combination surfactin with ampicillin showed a synergistic effect against P. aeruginosa ATCC 27853.

Microorganisms area treasure in terms of theproduction of various bioactive compounds which are being explored in different arenas of applied sciences. In agriculture, microbes and their bioactive compounds are being utilized in growth promotion and health promotion withnutrient fortification and its acquisition. Exhaustive explorations are unraveling the vast diversity of microbialcompounds with their potential usage in solving multiferous problems incrop production. Lipopeptides are one of such microbial compounds which havestrong antimicrobial properties against different plant pathogens. These compounds are reported to be produced by bacteria, cyanobacteria, fungi, and few other microorganisms; however, genus Bacillus alone produces a majority of diverse lipopeptides. Lipopeptides are low molecular weight compounds which havemultiple industrial roles apart from being usedas biosurfactants and antimicrobials. In plant protection, lipopeptides have wide prospects owing totheirpore...

Pedobacter cryoconitis strain UP508 was isolated from a soil sample using a mixture of ampicillin, kanamycin, and nalidixic acid for selection. UP508 was found to produce >30 unknown antibacterial peptides, of which eight, isopedopeptins A−H (1−8), were isolated by bioassay-guided fractionation and characterized with respect to structures and biological properties. Compounds 1−8 were all composed of nine amino acid residues and one 3-hydroxy fatty acid residue, and the structures were ring-closed via an ester bond from the C-terminal aspartic acid to the 3-hydroxy fatty acid. The differences between the peptides were the size and branching of the 3-hydroxy fatty acid and the presence of a valine or a 3-hydroxyvaline residue. The isopedopeptins mainly had activity against Gram-negative bacteria, and isopedopeptin B (2), which had the best combination of antibacterial activity, in vitro cytotoxicity, and hemolytic properties, was selected for further studies against a larger panel of Gram-negative bacteria. Isopedopeptin B was found to have good activity against strains of WHO top-priority Gram-negative bacteria, i.e., carbapenemresistant Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa, with minimal inhibitory concentrations (MIC) down to 1, 2, and 4 μg/mL, respectively. Furthermore, compound 2 had activity against colistin-resistant strains of A. baumannii, E. coli, and Klebsiella pneumoniae, with a MIC down to 8, 2, and 4 μg/mL, respectively. Compound 6 was tested in an E. coli liposome system where it induced significant leakage, indicating membrane disruption as one mechanism involved in isopedopeptin antibacterial activity. Isopedopeptin B stands out as a promising candidate for further studies with the goal to develop a new antibiotic drug.

Herein, a bactericide-secreting Bacillus strain, potentially useful as a biocontrol agent, was isolated from the commercial Yanjing Natto food. Following the biochemical and physiological evaluation, the molecular identification was performed using 16S rDNA sequencing of polymerase chain reaction-amplified DNA that confirmed the natto isolate as Bacillus subtilis natto (B. subtilis natto). The biocontrol (microbial inhibitory) capability of B. subtilis natto was investigated against Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and yeast (Yarrowia lipolytica) and recorded. The antimicrobial activity of B. subtilis natto was further enhanced by optimizing the growth medium for optimal bactericides secretion. Under optimized conditions, B. subtilis natto exhibited much higher inhibitory activity against S. aureus with a zone of inhibition diameter up to 27 mm. After 48 h incubation, the optimally yielded B. subtilis natto broth was used to extract and purify the res...

Surfactin is one of the most powerful biosurfactants that has been known so far. It is an acidic cyclic nonribosomal lipoheptapeptide that is produced by Bacillus subtilis. In this presentation we investigated different properties of surfactin C-15. The nanomicelle forming ability of surfactin C-15 in different aqueous environments with various ionic strengths was studied by scanning electron microscope. Surfactin second structure was investigated by Far-UV CD spectrum. Its hemolytic activity and cytotoxicity were measured by hemolysis and MTT assays, respectively. Surfactin formed spherical nanomicelles in distilled water (pH = 7.4) and amorphous nanomicelles in PBS buffer (pH = 7.4). The hemolysis assay results indicated that HC 50 of surfactin was 47 μM. Surfactin C-15 arrested growth of human cervix cancer HeLa cell line in a time-and dosage-dependent method, so that its IC 50 at 16, 24, and 48h were 86.9, 73.1, and 50.2 μM, respectively.

Aminoglycosides (Figure 1.1) were first established as antibiotics in the 1940s and are still widely used worldwide. They are obtained by fermentation of Streptomyces, Micromonospora, and Bacillus; irreversibly inhibit protein synthesis by acting on the ribosome; and are especially active against gram-negative bacteria. They chemically consist of an aminocyclitol substituted with amino sugars. A classification proposed by Umezawa was based on the central structure, which can be streptamine 1, 2-deoxystreptamine 2, or streptidine 3. A relevant number of natural and semisynthetic derivatives have been obtained since their discovery with the aim of bettering the toxicity issues linked to these structures, mainly oto-and nephrotoxicity, and to fight the increased resistance that mostly arises from structural modification of the

Antibiotics are considered as weapons against some diseases. The utilization of antibiotics over the last decades have generated a strong selective pressure for the emergence of multi-resistant strains and nosocomial infections. Biofilm phenotype was demonstrated as a key parameter in spreading infections, especially in hospitals and healthcare units. Biofilm phenotype was associated with a high tolerance to exogenous stress, and treatments with conventional antibiotics were usually ineffective at eradicating them. Thus, the development of novel anti-biofilm drugs is actually of the upmost importance. Here, the antimicrobial and anti-biofilm activities towards pathogenic microorganisms of a set of non-ribosomaly synthetized peptides and polyketides isolated from B. subtilis BG2571A culture supernatant were presented.

Cyclic lipopeptides (CLPs) are non-ribosomal biosurfactants produced by Bacillus species that exhibit outstanding interfacial activity. The synthesis of CLPs is under genetic and environmental influence, and representatives from different families are generally co-produced, generating isoforms that differ in chemical structure and biological activities. This study to evaluate the effect of low and high NaCl concentrations on the composition and surface activity of CLPs produced by Bacillus strains TIM27, TIM49, TIM68, and ICA13 towards microbial enhanced oil recovery (MEOR). The strains were evaluated in mineral medium containing NaCl 2.7, 66, or 100 g L-1 and growth, surface tension and emulsification activity were monitored. Based on the analysis of 16S rDNA, gyrB and rpoB sequences TIM27 and TIM49 were assigned to Bacillus subtilis, TIM68 to Bacillus vallismortis, and ICA13 to Bacillus amyloliquefaciens. All strains tolerated up to 100-g L-1 NaCl, but only TIM49 and TIM68 were ab...

Antimicrobial resistance is a major public health and development concern on a global scale. The increasing resistance of the pathogenic bacteria Neisseria gonorrhoeae to antibiotics necessitates efforts to identify potential alternative antibiotics from nature, including insects, which are already recognized as a source of natural antibiotics by the scientific community. This study aimed to determine the potential of components of gut-associated bacteria isolated from Apis dorsata, an Asian giant honeybee, as an antibacterial against N. gonorrhoeae by in vitro and in silico methods as an initial process in the stage of new drug discovery. The identified gut-associated bacteria of A. dorsata included Acinetobacter indicus and Bacillus cereus with 100% identity to referenced bacteria from GenBank. Cell-free culture supernatants (CFCS) of B. cereus had a very strong antibacterial activity against N. gonorrhoeae in an in vitro antibacterial testing. Meanwhile, molecular docking reveale...

The present study emphasizes the diversity assessment of marine Bacillus species with special reference to biosurfactant production, respective gene expression, and discrimination among Bacillus licheniformis and Bacillus subtilis. Among the 200 individual species of eastern coastal plain of Tamil Nadu screened, five biosurfactant producing potential bacterial species with entirely different morphology were selected. Biochemical and 16S rRNA gene sequence analysis suggested that all the said five species belong to Bacillus genera but differ in species levels. Biosurfactant of all the five species fluctuates in greater levels with respect to activity as well as to constituents but showed partial similarity to the commercially available surfactin. The expression of srf gene was realized in all of the five species. However, the sfp gene expression was observed only in three species. In conclusion, both B. licheniformis and B. subtilis demonstrate srf gene; nevertheless, sfp gene was expressed only by Bacillus subtilis.

Published Ahead of Print 27 May 2014. 10.1128/AAC.02536-13. 2014, 58(8):4420. DOI: Antimicrob. Agents Chemother. Marie-Paule Mingeot-Leclercq Bambeke, Julien M. Buyck, Jean-Luc Decout and Van Delbar, Luiza Souza Machado, Katy Jeannot, Françoise Guillaume Sautrey, Louis Zimmermann, Magali Deleu, Alicia Lipopolysaccharides aeruginosa and Their Interactions with Active against Resistant Pseudomonas New Amphiphilic Neamine Derivatives

Bacterial metabolites have been immensely useful as antibiotics, hence most of the work on the subject revolved around understanding their antibiotic properties. However, it emerged from current literature that they are pleotropic in nature as they express a broad array of activities with potential therapeutic significance. These characteristics include, but are not limited to anticancer, antiviral, antitrypanosomal, antidiabetic adjuvants, anti-inflammatory, hepatoprotective etc. A structural classification of the bacterial metabolites has been given based on the structures re-drawn from the published data. Role of the structural motifs, thought to be primarily present in fungal and plant (eukaryotic) metabolites but now reported in bacterial metabolites as well, have been discussed in light of their multifaceted activities. An analysis of the current literature pertaining to diverse therapeutic properties of the bacterial metabolites is presented.

Figure 1. (A) Five key features of the polymyxin molecule. Inset: Structure of Lipid A isolated from polymyxin-resistant P. aeruginosa showing the aminoarabinose (Ara4N) modifications. 16 (B) An SAR model of lipopeptide FADDI-002 complexed to Kdo2lipid A.

Biosurfactants are important in many areas; however, costs impede large-scale production. This work aimed to develop a global sustainable strategy for the production of biosurfactants by a novel strain of Bacillus amyloliquefaciens. Initially, Bacillus sp. strain 0G was renamed B. amyloliquefaciens subsp. plantarum (syn. Bacillus velezensis) after analysis of the gyrA and gyrB DNA sequences. Growth in modified Landy’s medium produced 3 main recoverable metabolites: surfactin, fengycin, and acetoin, which promote plant growth. Cultivation was studied in the presence of renewable carbon (as glycerol) and nitrogen (as arginine) sources. While diverse kinetics of acetoin production were observed in different media, similar yields (6–8 g·L–1) were obtained after 72 h of growth. Glycerol increased surfactin-specific production, while arginine increased the yields of surfactin and fengycin and increased biomass significantly. The specific production of fengycin increased ∼10 times, possibl...

Antimicrobial resistance is a major public health and development concern on a global scale. The increasing resistance of the pathogenic bacteria Neisseria gonorrhoeae to antibiotics necessitates efforts to identify potential alternative antibiotics from nature, including insects, which are already recognized as a source of natural antibiotics by the scientific community. This study aimed to determine the potential of components of gut-associated bacteria isolated from Apis dorsata, an Asian giant honeybee, as an antibacterial against N. gonorrhoeae by in vitro and in silico methods as an initial process in the stage of new drug discovery. The identified gut-associated bacteria of A. dorsata included Acinetobacter indicus and Bacillus cereus with 100% identity to referenced bacteria from GenBank. Cell-free culture supernatants (CFCS) of B. cereus had a very strong antibacterial activity against N. gonorrhoeae in an in vitro antibacterial testing. Meanwhile, molecular docking reveale...

Antimicrobial peptides of higher organisms have been studied for the past 25 years, and their importance as components of innate immunity is now well established. The essential simplicity of their chemical structure, along with the lower likelihood of developed resistance compared to conventional antibiotics, has made them attractive candidates for development as therapeutics. The objective of this review article is to describe the current relevance, main mechanisms presented, and the uses of antimicrobial peptides as new therapies in the clinical area. The information used was mainly compiled from scientific articles based on a systematic review of scientific papers with data on human antimicrobial peptides (AMPs) and their different applications, searching without date limits and only documents in English and Spanish. Gray literature was accessed through manual search, and no restrictions were made involving study design for a retrospective study. Although these products have not ...

We describe a primary high-throughput screen that uses the reporter strain Bacillus subtilis BAU-102 to identify antibiotics that induce autolysis. The screen measures autolysis in terms of the incipient release of recombinant Escherichia coli ␤-galactosidase (␤-Gal) from the periplasmic space of B. subtilis owing to a loss of integrity of the cell wall. In a model screen, ␤-Gal release values for 79 members of a library consisting of antibiotics and related compounds were collected, sorted, and plotted as a function of rank. Inducers of autolysis, which included compounds that inhibit cell wall synthesis and those that do not, were readily differentiated from other members of the library on the basis of their elevated ␤-galactosidase release responses. The results of the BAU-102 model screen called attention to the antibacterial activity of drugs normally used in other applications, describable as "repurposed." Thus, the screen independently identified the potential antibacterial properties of the antifungal drug miconazole and of the antileishmaniasis drug miltefosine. Daptomycin-induced release of ␤-Gal was also detected and occurred in a Ca 2؉-dependent manner.

Surfactin lipopeptide (SLP) from Bacillus subtilis KLP2015 (Accession number KT459335) was extracted and purified by ammonium sulphate precipitation, DEAE and size exclusion chromatography. The molecular mass of the purified Surfactin lipopeptide was determined ~ 1000 Dalton through ESI-MS and MALDI-TOF-MS/MS analysis. The purified Surfactin possessed a strong cytotoxicity towards tested mammalian cancer cells HCT-15, Hep2-C, L-132, MCF-7 and NIH/3T3 with the percentage cell death of 80.1 ± 1.92%, 76.09 ± 1.32%, 88.56 ± 2.41%, 78.91 ± 2.09% and 77.84 ± 1.96% respectively and less cytotoxicity to normal HaCaT cells (31.45 ± 2.58%). A fivefold decrease in DNA content was noted in LP treated L-132 cells while twofold in Hep2-C after 20 h while, SDS treated L-132 and Hep2-C cells showed approximate 1.5 and 1.4-fold decrease in DNA content from its initial. The antibacterial assay using purified LP (concentration, 50 µg/well) of B. subtilis KLP2015 exhibited marked inhibtion of Klebsiella pnemoniae (15.0 ± 0.4 mm), Salmonella typhimurium NCTC 74 (13.0 ± 0.2 mm), Staphylococcus aureus ATCC 6538(12.0 ± 0.3 mm) and Escherichia coli NCTC 10418(8.0 ± 0.7 mm). The dislodging of biofilms formation was observed in all the 7 tested strains except Shigella flexneri. The maximum process of biofilm formation was reduced by 58% in case of S. aureus ATCC 6538.

A lot of crops are destroyed by the phytopathogens such as fungi, bacteria, and yeast leading to economic losses to the farmers. Members of theBacillusgenus are considered as the factories for the production of biologically active molecules that are potential inhibitors of growth of phytopathogens. Plant diseases constitute an emerging threat to global food security. Many of the currently available antimicrobial agents for agriculture are highly toxic and nonbiodegradable and thus cause extended environmental pollution. Moreover, an increasing number of phytopathogens have developed resistance to antimicrobial agents. The lipopeptides have been tried as potent versatile weapons to deal with a variety of phytopathogens. All the three families ofBacilluslipopeptides, namely, Surfactins, Iturins and Fengycins, have been explored for their antagonistic activities towards a wide range of phytopathogens including bacteria, fungi, and oomycetes. Iturin and Fengycin have antifungal activiti...

Anopheles stephensi vector of a Plasmodium parasite which are responsible for spreading malaria in modern world. 30 Presently, malaria suppression is desirable one because of insecticide resistance nature of vector, specifically 31 improvement of Plasmodium species as highly resistant to a many antimalarial drugs. Present study focused as 32 biosurfactant production using two potential biosurfactant producing bacterial strains such as Bacillus subtilis A1 33 and Pseudomonas stutzeri NA3 for mosquitocidal application. Produced biosurfactant were characterized using 34 fourier transform infrared (FTIR) spectroscopy and gas chromatography and mass spectrometry (GCMS) and 35 confirmed that the produced biosurfactant were lipopeptide in nature. Different concentration of the biosurfactant 36 ranged between 2-10 ppm was tested against different stages of A. stephensi and both biosurfactant were found as 37 exterminating larval and pupal stages of mosquitoes. LC50 values were 3.58 (I), 4.92 (II), 5.73 (III), 7.10 (IV) and 38 7.99 (pupae) and 2.61 (I), 3.68 (II), 4.48 (III), 5.55 (IV) and 6.99 (pupa) for biosurfactant produced by B. subtilis A1 39 and P. stutzeri NA3 respectively. Biosurfactant are eco-friendly and easily producible using low cost material. The 40 toxic nature of these biosurfactant to the targeted organism like A. stephensi is lead to promising application in the 41 medical field.