Effect of Co-inhabiting Coagulase Negative Staphylococci on S. aureus agr Quorum Sensing, Host Factor Binding, and Biofilm Formation

Abstract

Staphylococcus aureus is a commensal colonizer of both humans and animals, but also an opportunistic pathogen responsible for a multitude of diseases. In recent years, colonization of pigs by methicillin resistant S. aureus has become a problem with increasing numbers of humans being infected by livestock strains. In S. aureus colonization and virulence factor expression is controlled by the agr quorum sensing system, which responds to and is activated by self-generated, autoinducing peptides (AIPs). AIPs are also produced by coagulase negative staphylococci (CoNS) commonly found as commensals in both humans and animals, and interestingly, some of these inhibit S. aureus agr activity. Here, we have addressed if cross-communication occurs between S. aureus and CoNS strains isolated from pig nares, and if so, how properties such as host factor binding and biofilm formation are affected. From 25 pig nasal swabs we obtained 54 staphylococcal CoNS isolates belonging to 8 different species. Of these, none were able to induce S. aureus agr as monitored by reporter gene fusions to agr regulated genes but a number of agr-inhibiting species were identified including Staphylococcus hyicus, Staphylococcus simulans, Staphylococcus arlettae, Staphylococcus lentus, and Staphylococcus chromogenes. After establishing that the inhibitory activity was mediated via AgrC, the receptor of AIPs, we synthesized selective AIPs to explore their effect on adhesion of S. aureus to fibronectin, a host factor involved in S. aureus colonization. Here, we found that the CoNS AIPs did not affect adhesion of S. aureus except for strain 8325-4. When individual CoNS strains were co-cultured together with S. aureus we observed variable degrees of biofilm formation which did not correlate with agr interactions. Our results show that multiple CoNS species can be isolated from pig nares and that the majority of these produce AIPs that inhibit S. aureus agr. Further they show that the consequences of the interactions between CoNS and S. aureus are complex and highly strain dependent.

Molecular Epidemiology of Staphylococcus aureus Lineages in Wild Animals in Europe: A Review

“…The agr locus consists of four genes: agrB encodes a membrane protein responsible for translocation and modification of AgrD; agrD encodes an AIP precursor octapeptide; agrC encodes a membrane receptor protein of the AIP signal and agrA encodes the AgrA response regulator that activates transcription. agr varies between S. aureus strains and can be divided into four groups (agr type I, II, III and IV) [70]. Studies have reported the association between the agr types and the different clonal lineages, antibiotic resistance profile, biofilm formation, the toxins produced and their link with diseases [71].…”

“…Studies have reported the association between the agr types and the different clonal lineages, antibiotic resistance profile, biofilm formation, the toxins produced and their link with diseases [71]. For instance, agr type I and II strains are usually associated with endocarditis and septicemia whereas agr type III and IV strains are associated with TSST-1, exfoliative syndromes and bullous impetigo [70].…”

“…CA-MRSA mainly belong to clonal complexes CC8 (ST8), CC30 (ST30), CC59, CC80 and CC93; HA-MRSA are mainly assigned to CC5, CC8 (ST239), CC22, CC30 (ST36) and CC45; and LA-MRSA are mostly ascribed to CC398 [79]. Moreover, certain S. aureus clonal lineages correlate with different agr types: clonal lineages CC8, CC25, CC22, CC45, and CC395 are usually associated with agr type I; CC5, CC12, and CC15 with agr type II; CC30 is often characterized by agr type III, and CC121 by agr type IV [70].…”

Novel Peptide from Commensal Staphylococcus simulans Blocks Methicillin-Resistant Staphylococcus aureus Quorum Sensing and Protects Host Skin from Damage

“…Each agr type specifically responds to its cognate AIP signal, and intraspecies cross talk between noncognate S. aureus agr types has been extensively characterized (30). Furthermore, there are now several examples of human-and animal-derived CoNS AIPs that inhibit S. aureus quorum sensing via interspecies cross talk (12,(31)(32)(33)(34). For example, quorum sensing interference by the rare skin commensal Staphylococcus caprae attenuated acute MRSA skin infection and also limited initial MRSA skin colonization (11).…”

Evolving concepts and emerging solutions to the problem of staphylococcal infection in dermatology

“…Бурцева, М.А. Сергеева на у S. lugdunensis [25], губительно действующих на S. aureus, эти виды (S. epidermidis и S. caprae) могут подавлять «чувство кворума» и агрессию золотистого стафилококка, в том числе за счет неродственных аутоиндуцирующих пептидов [26,27,28]. Важными считаются выработка толерантности иммунитета к стафилококкам постоянными и разнообразными компонентами микробиома (S. epidermidis и другие комменсалы) начиная с первых лет жизни, а также «тренировка» особых иммунокомпетентных клеток в зрелом возрасте, способствующая, в том числе, образованию противомикробных пептидов [29].…”