Underexplored bacteria as reservoirs of novel antimicrobial lipopeptides

Abstract

Natural products derived from microorganisms play a prominent role in drug discovery as potential anti-infective agents. Over the past few decades, lipopeptides produced by particularly Bacillus, Pseudomonas, Streptomyces, Paenibacillus, and cyanobacteria species, have been extensively studied for their antimicrobial potential. Subsequently, daptomycin and polymyxin B were approved by the Food and Drug Administration as lipopeptide antibiotics. Recent studies have however, indicated that Serratia, Brevibacillus, and Burkholderia, as well as predatory bacteria such as Myxococcus, Lysobacter, and Cystobacter, hold promise as relatively underexplored sources of novel classes of lipopeptides. This review will thus highlight the structures and the newly discovered scaffolds of lipopeptide families produced by these bacterial genera, with potential antimicrobial activities. Additionally, insight into the mode of action and biosynthesis of these lipopeptides will be provided and the application of a genome mining approach, to ascertain the biosynthetic gene cluster potential of these bacterial genera (genomes available on the National Center for Biotechnology Information) for their future pharmaceutical exploitation, will be discussed.

Characterization of Bacillus Strains from Natural Honeybee Products with High Keratinolytic Activity and Antimicrobial Potential

“…For example, it was shown that some Bacillus species, present in the gut of honeybees, were able to kill the pathogenic Paenibacillus larvae , which is the causative agent of foulbrood disease in bees, providing further indications that the bacteria within the honeybee microbiome may exhibit antimicrobial properties [ 49 ]. Actually, Bacillus species are an important source of antibiotics [ 50 ]. Some of these antimicrobial compounds are lipopeptides, which are produced by NRPS encoded in clusters on the bacterial genome [ 50 ].…”

“…Actually, Bacillus species are an important source of antibiotics [ 50 ]. Some of these antimicrobial compounds are lipopeptides, which are produced by NRPS encoded in clusters on the bacterial genome [ 50 ]. Lipopeptides, that act through the disruption of membranes, are a particularly important source of antimicrobials, as it is less likely that resistance will develop towards them compared to other antibiotics.…”

Genome-driven discovery of new serrawettin W2 analogues from Serratia fonticola DSM 4576

“…8,9 Given that Serratia possesses an abundance of nonribosomal peptide synthetase (NRPS) BGCs, there is untapped potential for exploring bioactive peptides within this genus. 10 NRPSs are large multimodular enzymes that assemble amino acids into diverse peptides through various modifications, such as cyclization, methylation, and glycosylation. 11,12 NRPS-derived lipopeptides are characterized by a hydrophilic peptide head group linked to a hydrophobic fatty acid tail, resulting in their amphiphilic nature.…”

“…13 One of the typical lipopeptides produced by Serratia species is serrawettin W2, which is a cyclic lipopeptide composed of five amino acids (Leu-Ser-Thr-Phe-Ile) and a C 10 fatty acid chain. 10,14 Serrawettin W2 exhibits antimicrobial activity against Gram-positive and Gramnegative bacteria, such as methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. 15,16 However, to the best of our knowledge, there is no report on the discovery of NRPs from Serratia via genome mining approaches.…”

“…8,9 Given that Serratia possesses an abundance of nonribosomal peptide synthetase (NRPS) BGCs, there is untapped potential for exploring bioactive peptides within this genus. 10…”