Staphylococcus epidermidis MSCRAMM SesJ Is Encoded in Composite Islands

Abstract

Staphylococcus epidermidis is a leading cause of nosocomial infections in patients with a compromised immune system and/or an implanted medical device. Seventy to 90% of S. epidermidis clinical isolates are methicillin resistant and carry the mecA gene, present in a mobile genetic element (MGE) called the staphylococcal cassette chromosome mec (SCCmec) element. Along with the presence of antibiotic and heavy metal resistance genes, MGEs can also contain genes encoding secreted or cell wall-anchored virulence factors. In our earlier studies of S. epidermidis clinical isolates, we discovered S. epidermidis surface protein J (SesJ), a prototype of a recently discovered subfamily of the microbial surface component recognizing adhesive matrix molecule (MSCRAMM) group. MSCRAMMs are major virulence factors of pathogenic Gram-positive bacteria. Here, we report that the sesJ gene is always accompanied by two glycosyltransferase genes, gtfA and gtfB, and is present in two MGEs, called the arginine catabolic mobile element (ACME) and the staphylococcal cassette chromosome (SCC) element. The presence of the sesJ gene was associated with the left-hand direct repeat DR_B or DR_E. When inserted via DR_E, the sesJ gene was encoded in the SCC element. When inserted via DR_B, the sesJ gene was accompanied by the genes for the type 1 restriction modification system and was encoded in the ACME. Additionally, the SCC element and ACME carry different isoforms of the SesJ protein. To date, the genes encoding MSCRAMMs have been seen to be located in the bacterial core genome. Here, we report the presence of an MSCRAMM in an MGE in S. epidermidis clinical isolates. IMPORTANCE S. epidermidis is an opportunistic bacterium that has established itself as a successful nosocomial pathogen. The modern era of novel therapeutics and medical devices has extended the longevity of human life, but at the same time, we also witness the evolution of pathogens to adapt to newly available niches in the host. Increasing antibiotic resistance among pathogens provides an example of such pathogen adaptation. With limited opportunities to modify the core genome, most of the adaptation occurs by acquiring new genes, such as virulence factors and antibiotic resistance determinants present in MGEs. In this study, we describe that the sesJ gene, encoding a recently discovered cell wall-anchored protein in S. epidermidis, is present in both ACME and the SCC element. The presence of virulence factors in MGEs can influence the virulence potential of a specific strain. Therefore, it is critical to study the virulence factors found in MGEs in emerging pathogenic bacteria or strains to understand the mechanisms used by these bacteria to cause infections.

Surface Proteins of Staphylococcus epidermidis

“…The genes encoding the SesJ protein and its associated glycosyl transferases are located within SCC mobile genetic elements (Arora et al, 2020). The sesJ gene is present in about 18% of disease isolates from several different STs including ST2 that were isolated in two American hospitals.…”

“…However, the N1 subdomain is shorter than that of SdrG and SdrF. The A region occurs in two isoforms that are 95% identical (Arora et al, 2020). This is followed by two B repeats which are similar in sequence and predicted structure to the B repeats of SdrG and SdrF.…”

“…Studies to identify the ligand(s) recognized by SesJ have been inconclusive (Arora et al, 2020). The recombinant A domain did not bind to fibrinogen, fibronectin, laminin, vitronectin, and several types of collagen.…”

“…The majority of genes encoding members of the MSCRAMM family of CWA proteins of S. epidermidis are present in the core genome ( Conlan et al, 2012 ). A notable exception is sesJ which is carried by SCC mec or ACME mobile genetic elements ( Arora et al, 2020 ). SesJ was present in about 18% of clinical isolates from bloodstream infections collected in two US hospitals.…”

“…Genome wide association studies of commensal and disease isolates identified infection-associated genetic sequences in loci associated with biofilm formation, toxicity, inflammation, and resistance to antibiotics ( Meric et al, 2018 ). Whole genes and short sequences carrying allelic variations within genes have been transmitted by chromosomal recombination, while entire SCC mec elements encoding β-lactam resistance and potential virulence determinants ( Qin et al, 2017 ; Arora et al, 2020 ) have been transmitted horizontally. It was concluded that many strains from the two clades can cause disease.…”