Therapeutic cyclic lipopeptides mining from microbes: latest strides and hurdles

Abstract

Infectious diseases impose serious public health burdens and often have devastating consequences. The cyclic lipopeptides elaborated by bacteria Bacillus, Paenibacillus, Pseudomonas, Streptomyces, Serratia, Propionibacterium and fungus Fusarium are very crucial in restraining the pathogens. Composed of a peptide and a fatty acyl moiety these amphiphilic metabolites exhibit broad spectrum antimicrobial effects. Among the plethora of cyclic lipopeptides, only selective few have emerged as robust antibiotics. For their functional vigor, polymyxin, daptomycin, surfactin, iturin, fengysin, paenibacterin and pseudofactin have been integrated in mainstream healthcare. Daptomycin has been a significant part of antimicrobial arsenal since the past decade. As the magnitude of drug resistance rises in unprecedented manner, the urgency of prospecting novel cyclic lipopeptides is being perceived. Intense research has revealed the implication of these bioactive compounds stretching beyond antibacterial and antifungal. Anticancer, immunomodulatory, prosthetic parts disinfection and vaccine adjuvancy are some of the validated prospects. This review discusses the emerging applications, mechanisms governing the biological actions, role of genomics in refining structure and function, semi-synthetic analog discovery, novel strain isolation, setbacks etc. Though its beyond the scope of the current topic, for holistic purpose, the role of lipopeptides in bioremediation and crop biotechnology has been briefly outlined. This updated critique is expected to galvanize innovations and diversify therapeutic recruitment of microbial lipopeptides.

Mast cells partially contribute to mucosal adjuvanticity of surfactin in mice

“…We reasoned that the extent of mast cell activation and adjuvanticity of compounds such as SF and PMB might be interrelated. One major difference between SF and PMB chemical structures is the length of alkyl chain: 11 and 6–7 carbon atoms, respectively . Indeed, when the release of histamine from mast cells was induced by parabens with different alkyl chains, ranging from methylparaben to dodecylparaben, a complex relationship was observed between the extent of mast cell activation and the length of alkyl chain .…”

“…Therefore, elucidating the immunological mechanism of SF adjuvanticity is important. We noted that SF, PMB, and CL share a common structural element consisting of a cyclic heptapeptide bound to a fatty acid chain . Because the structure of SF is similar to those of PMB and CL, it was expected that SF would activate mast cells and, as a result, enhance Ag‐specific immune responses.…”

Fighting bacterial resistance: approaches, challenges, and opportunities in the search for new antibiotics.Part 1. Antibiotics used in clinical practice: mechanisms of action and the development of bacterial resistance

“…There are several known active lipopeptide antimicrobials and at least three of them -polymyxin B, polymyxin E (colistin) (Fig. 46) [109], and daptomycin (Fig. 47) [109] -are or have been in clinical practice.…”

Critical micelle concentration and particle size determine adjuvanticity of cyclic lipopeptides

“…polymyxa subspecies colistinus , B. amyloliquefaciens and B. subtilis , respectively. These polypeptide compounds have an amphiphilic structure with a hydrophilic head moiety and an alkyl chain as a hydrophobic tail moiety . Amphiphilic molecules are commonly tensioactive .…”

“…These polypeptide compounds have an amphiphilic structure with a hydrophilic head moiety and an alkyl chain as a hydrophobic tail moiety. 9 Amphiphilic molecules are commonly tensioactive. 10 SF was shown to have a stronger surface activity than sodium dodecyl sulfate, a synthetic surfactant.…”