Sublancin protects against methicillin-resistant Staphylococcus aureus infection by the combined modulation of innate immune response and microbiota

Ribosomally synthesized peptides, foreground players in microbial interactions: recent developments and unanswered questions

“…As reviewed extensively, 42–44 these modifications largely expand the chemical diversity of RSPs, far beyond the twenty canonical amino acids. They include, among the most widespread, the formation of intramolecular thioether bridges in lanthipeptides, 45–47 formation of thiazol(in)e and/or (methyl)oxazol(in)e heterocycles in linear azol(in)e-containing peptides (LAPs), 48,49 or formation of new C–C bonds through different chemistries, such as in cyclophanes. 44,50 Cyclizations, either of N-terminus to C-terminus type (head-to-tail), or of N-terminus to side-chain carboxylate type to form a macrolactam ring, also occur as primary PTMs, thus providing circular bacteriocins 51,52 and lasso peptides, 53 respectively.…”

“…However, other bacteriocins are much more extensively modified, such as lanthipeptides which are probably the most studied RiPPs from LAB. 44,45,47,67 They are characterized by sulfur to β-carbon thioether cross-links (lanthionine rings) and include lantibiotics, a class of lanthipeptides with antimicrobial activity. The most popular and archetypical lantibiotic is nisin, produced by Lactococcus lactis , which is used as a food preservative (Nisaplin R , Niprosin R ) in more than eighty countries for more than fifty years and has prompted an extraordinary number of studies (Fig.…”

“…4) produced by Bacillus subtilis 168, was shown to modulate the microbiota community to outcompete methicillin-resistant Staphylococcus aureus (MRSA) and protect the host against infection in a mouse infection model. 47 Sublancin can ameliorate the microbiota composition and its metabolic activity following the dysbiosis induced by the pathogen. Moreover, it simultaneously stimulates the innate response of the host, thus more efficiently protecting it.…”

Efficiency of Antimicrobial Peptides Against Multidrug-Resistant Staphylococcal Pathogens

“…Mersacidin, a lantibiotic produced by Bacillus sp., was shown to eradicate the colonization of human-derived MRSA in a mouse rhinitis model ( Kruszewska et al, 2004 ). Sublancin, a glycosylated AMP produced by B. subtilis , exhibited antibacterial and immunomodulatory effects against a MRSA-infected mouse model that induced intraperitoneal ( Wang et al, 2017 ; Li et al, 2021 ) or intestinal injury ( Wang et al, 2014 ). K2A and R13A, two analogues of mutacin 1,140, have been reported to improve pharmacokinetics in vivo and efficiently rescue mice infected with MRSA at 10 mg/kg (100% protection) or 2.5 mg/kg (50% protection; Geng et al, 2018 ).…”

Characterization of subtilosin gene in wild type Bacillus spp. and possible physiological role

“…They are members of both classes: the ribosomally synthesized e.g. subtilin 2 , Ericin 3 and sublancin 4 and the nonribosomally synthesized such as the lipopeptides surfactin 5 , 6 , mycosubtilin 7 , and fengycin 8 Bacilysocin 9 and 3,3'-Neotrehalosadiamine 10 . Subtilosin A is one of many antibiotics produced by Bacillus strains 11 , 12 its importance and role in Bacillus group is little understood.…”