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Autolysins are endogenous lytic enzymes that break down the peptidoglycan components of biological cells which enables the separation of daughter cells following cell division. They are involved in cell growth, cell wall metabolism, cell division and separation, as well as peptidoglycan turnover and have similar functions to lysozymes.
A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular polymeric substances (EPSs). The cells within the biofilm produce the EPS components, which are typically a polymeric conglomeration of extracellular polysaccharides, proteins, lipids and DNA. Because they have three-dimensional structure and represent a community lifestyle for microorganisms, they have been metaphorically described as "cities for microbes".
Staphylococcus aureus is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive for catalase and nitrate reduction and is a facultative anaerobe that can grow without the need for oxygen. Although S. aureus usually acts as a commensal of the human microbiota, it can also become an opportunistic pathogen, being a common cause of skin infections including abscesses, respiratory infections such as sinusitis, and food poisoning. Pathogenic strains often promote infections by producing virulence factors such as potent protein toxins, and the expression of a cell-surface protein that binds and inactivates antibodies. S. aureus is one of the leading pathogens for deaths associated with antimicrobial resistance and the emergence of antibiotic-resistant strains, such as methicillin-resistant S. aureus (MRSA), is a worldwide problem in clinical medicine. Despite much research and development, no vaccine for S. aureus has been approved.
Staphylococcus haemolyticus is a member of the coagulase-negative staphylococci (CoNS). It is part of the skin flora of humans, and its largest populations are usually found at the axillae, perineum, and inguinal areas. S. haemolyticus also colonizes primates and domestic animals. It is a well-known opportunistic pathogen, and is the second-most frequently isolated CoNS. Infections can be localized or systemic, and are often associated with the insertion of medical devices. The highly antibiotic-resistant phenotype and ability to form biofilms make S. haemolyticus a difficult pathogen to treat. Its most closely related species is Staphylococcus borealis.
Staphylococcus epidermidis is a Gram-positive bacterium, and one of over 40 species belonging to the genus Staphylococcus. It is part of the normal human microbiota, typically the skin microbiota, and less commonly the mucosal microbiota and also found in marine sponges. It is a facultative anaerobic bacteria. Although S. epidermidis is not usually pathogenic, patients with compromised immune systems are at risk of developing infection. These infections are generally hospital-acquired. S. epidermidis is a particular concern for people with catheters or other surgical implants because it is known to form biofilms that grow on these devices. Being part of the normal skin microbiota, S. epidermidis is a frequent contaminant of specimens sent to the diagnostic laboratory.
RNAIII is a stable 514 nt regulatory RNA transcribed by the P3 promoter of the Staphylococcus aureus quorum-sensing agr system ). It is the major effector of the agr regulon, which controls the expression of many S. aureus genes encoding exoproteins and cell wall associated proteins plus others encoding regulatory proteins The RNAIII transcript also encodes the 26 amino acid δ-haemolysin peptide (Hld). RNAIII contains many stem loops, most of which match the Shine-Dalgarno sequence involved in translation initiation of the regulated genes. Some of these interactions are inhibitory, others stimulatory; among the former is the regulatory protein Rot. In vitro, RNAIII is expressed post exponentially, inhibiting translation of the surface proteins, notably protein A, while stimulating that of the exoproteins, many of which are tissue-degrading enzymes or cytolysins. Among the latter is the important virulence factor, α-hemolysin (Hla), whose translation RNAIII activates by preventing the formation of an inhibitory foldback loop in the hla mRNA leader.
mecA is a gene found in bacterial cells which allows them to be resistant to antibiotics such as methicillin, penicillin and other penicillin-like antibiotics.
Sortase refers to a group of prokaryotic enzymes that modify surface proteins by recognizing and cleaving a carboxyl-terminal sorting signal. For most substrates of sortase enzymes, the recognition signal consists of the motif LPXTG (Leu-Pro-any-Thr-Gly), then a highly hydrophobic transmembrane sequence, followed by a cluster of basic residues such as arginine. Cleavage occurs between the Thr and Gly, with transient attachment through the Thr residue to the active site Cys residue, followed by transpeptidation that attaches the protein covalently to cell wall components. Sortases occur in almost all Gram-positive bacteria and the occasional Gram-negative bacterium or Archaea, where cell wall LPXTG-mediated decoration has not been reported. Although sortase A, the "housekeeping" sortase, typically acts on many protein targets, other forms of sortase recognize variant forms of the cleavage motif, or catalyze the assembly of pilins into pili.
Rsa RNAs are non-coding RNAs found in the bacterium Staphylococcus aureus. The shared name comes from their discovery, and does not imply homology. Bioinformatics scans identified the 16 Rsa RNA families named RsaA-K and RsaOA-OG. Others, RsaOH-OX, were found thanks to an RNomic approach. Although the RNAs showed varying expression patterns, many of the newly discovered RNAs were shown to be Hfq-independent and most carried a C-rich motif (UCCC).
Holins are a diverse group of small proteins produced by dsDNA bacteriophages in order to trigger and control the degradation of the host's cell wall at the end of the lytic cycle. Holins form pores in the host's cell membrane, allowing lysins to reach and degrade peptidoglycan, a component of bacterial cell walls. Holins have been shown to regulate the timing of lysis with great precision. Over 50 unrelated gene families encode holins, making them the most diverse group of proteins with common function. Together with lysins, holins are being studied for their potential use as antibacterial agents.
The Phi11 Holin Family constitutes the Holin Superfamily I.
The Monovalent Cation (K+ or Na+):Proton Antiporter-3 (CPA3) Family (TC# 2.A.63) is a member of the Na+ transporting Mrp superfamily. The CPA3 family consists of bacterial multicomponent K+:H+ and Na+:H+ antiporters. The best characterized systems are the PhaABCDEFG system of Sinorhizobium meliloti (TC# 2.A.63.1.1) that functions in pH adaptation and as a K+ efflux system, and the MnhABCDEFG system of Staphylococcus aureus (TC# 2.A.63.1.3) that functions as a Na+ efflux Na+:H+ antiporter.
The T4 Holin Family is a group of putative pore-forming proteins that does not belong to one of the seven holin superfamilies. T-even phage such as T4 use a holin-endolysin system for host cell lysis. Although the endolysin of phage T4 encoded by the e gene was identified in 1961, the holin was not characterized until 2001. A representative list of proteins belonging to the T4 holin family can be found in the Transporter Classification Database.
The SPP1 Holin Family consists of proteins of between 90 and 160 amino acyl residues (aas) in length that exhibit two transmembrane segments (TMSs). SPP1 is a double-stranded DNA phage that infects the Gram-positive bacteria. Although annotated as holins, members of the SPP1 family are not yet functionally characterized. A representative list of proteins belonging to the SPP1 Holin family can be found in Transporter Classification Database.
The Staphylococcusphage P68 Putative Holin Family consists of a single putative holin from Staphylococcus aureus phage P68 that is 92 amino acyl residues (aas) in length and exhibits 2 transmembrane segments (TMSs). While annotated as a holin, this protein has not been functionally characterized.[2]
Gene transfer agent-release holins are holins which are believed to facilitate the lysis-dependent release of a gene transfer agent. Particularly the gene transfer agent of Rhodobacter capsulatus (RcGTA), which is known to be a bacteriophage-like genetic element that induces horizontal gene transfer. The promoter of the RcGTA gene was identified by Westbye et al. in 2013. A representative list of members belonging to the GTA-Hol family can be found in the Transporter Classification Database with homologues found in Pseudomonadota and caudovirales.
The Brachyspira holin (B-Hol) Family consists of several proteins from the GTA holin of Brachyspira hyodysenteriae, which facilitates gene transfer agent-release to VSH-1 holin of Brachyspira pilosicoli. VSH-1 is thought to participate in cell lysis. These proteins range in size from about 85 to 145 amino acyl residues (aas) and exhibit between 2 and 4 transmembrane segments (TMSs). A representative list of proteins belonging to the B-Hol family can be found in the Transporter Classification Database.
Glutamyl endopeptidase I is a family of extracellular bacterial serine proteases. The proteases within this family have been identified in species of Staphylococcus, Bacillus, and Streptomyces, among others. The two former are more closely related, while the Streptomyces-type is treated as a separate family, glutamyl endopeptidase II.
CsgD is a transcription and response regulator protein referenced to as the master modulator of bacterial biofilm development. In E. coli cells, CsgD is tasked with aiding the transition from planktonic cell motility to the stationary phase of biofilm formation, in response to environmental growth factors. A transcription analysis assay illustrated a heightened decrease in CsgD's DNA-binding capacity when phosphorylated at A.A. D59 of the protein's primary sequence. Therefore, in the protein's active form (unphosphorylated), CsgD is capable of carrying out its normal functions of regulating curli proteins (fimbria) and producing ECM polysaccharides (cellulose). Following a promoter-lacZ fusion assay of CsgD binding to specific target sites on E. coli's genome, two classes of binding targets were identified: group I genes and group II genes. The group I genes, akin to fliE and yhbT, exhibit repressed transcription following their interaction with CsgD, whilst group II genes, including yccT and adrA, illustrated active functionality. Other group I operons that illustrate repressed transcription include fliE and fliEFGH, for motile flagellum formation. Other group II genes, imperative to the transition towards stationary biofilm development, include csgBA, encoding for curli fimbriae, and adrA, encoding for the synthesis of cyclic diguanylate. In this context, c-di-GMP functions as a bacterial secondary messenger, enhancing the production of extracellular cellulose and impeding flagellum production and rotation.
Accessory gene regulator (agr) is a complex 5 gene locus that is a global regulator of virulence in Staphylococcus aureus. It encodes a two-component transcriptional quorum-sensing (QS) system activated by an autoinducing, thiolactone-containing cyclic peptide (AIP).
References
- ↑ Ranjit, Dev K.; Endres, Jennifer L.; Bayles, Kenneth W. (2011-05-01). "Staphylococcus aureus CidA and LrgA proteins exhibit holin-like properties". Journal of Bacteriology. 193 (10): 2468–2476. doi:10.1128/JB.01545-10. ISSN 1098-5530. PMC 3133170 . PMID 21421752.
- ↑ Bayles, Kenneth W. (2003-07-01). "Are the molecular strategies that control apoptosis conserved in bacteria?". Trends in Microbiology. 11 (7): 306–311. doi:10.1016/s0966-842x(03)00144-6. ISSN 0966-842X. PMID 12875813.
- ↑ Yang, Soo-Jin; Rice, Kelly C.; Brown, Raquel J.; Patton, Toni G.; Liou, Linda E.; Park, Yong Ho; Bayles, Kenneth W. (2005-09-01). "A LysR-type regulator, CidR, is required for induction of the Staphylococcus aureus cidABC operon". Journal of Bacteriology. 187 (17): 5893–5900. doi:10.1128/JB.187.17.5893-5900.2005. ISSN 0021-9193. PMC 1196168 . PMID 16109930.
- ↑ Sharma-Kuinkel, Batu K.; Mann, Ethan E.; Ahn, Jong-Sam; Kuechenmeister, Lisa J.; Dunman, Paul M.; Bayles, Kenneth W. (2009-08-01). "The Staphylococcus aureus LytSR two-component regulatory system affects biofilm formation". Journal of Bacteriology. 191 (15): 4767–4775. doi:10.1128/JB.00348-09. ISSN 1098-5530. PMC 2715716 . PMID 19502411.
- ↑ Moormeier, Derek E.; Endres, Jennifer L.; Mann, Ethan E.; Sadykov, Marat R.; Horswill, Alexander R.; Rice, Kelly C.; Fey, Paul D.; Bayles, Kenneth W. (2013-06-01). "Use of microfluidic technology to analyze gene expression during Staphylococcus aureus biofilm formation reveals distinct physiological niches". Applied and Environmental Microbiology. 79 (11): 3413–3424. doi:10.1128/AEM.00395-13. ISSN 1098-5336. PMC 3648040 . PMID 23524683.
- ↑ Ahn, Sang-Joon; Qu, Ming-Da; Roberts, Elisha; Burne, Robert A.; Rice, Kelly C. (2012-01-01). "Identification of the Streptococcus mutans LytST two-component regulon reveals its contribution to oxidative stress tolerance". BMC Microbiology. 12: 187. doi:10.1186/1471-2180-12-187. ISSN 1471-2180. PMC 3507848 . PMID 22937869.
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