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Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia.

ABSTRACT: The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.

SUBMITTER: Douglas EJA

PROVIDER: S-EPMC9980097 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia.

Douglas Edward J A EJA Palk Nathanael N Brignoli Tarcisio T Altwiley Dina D Boura Marcia M Laabei Maisem M Recker Mario M Cheung Gordon Y C GYC Liu Ryan R Hsieh Roger C RC Otto Michael M O'Brien Eoin E McLoughlin Rachel M RM Massey Ruth C RC

bioRxiv : the preprint server for biology 20230424

The bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we ...[more]

PMID: 36865143

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Project description:Staphylococcus aureus bacteraemia is a serious infection associated with significant complications, including recurrence of bacteraemia, endocarditis and metastatic foci of infection. The management of these patients is often complex, involving appropriate source control, a thorough review and investigations to exclude metastatic foci and infective endocarditis. Additionally, a prolonged course of intravenous antibiotics is often required. As part of our quality improvement project, the following five aspects were evaluated in 56 patients with S. aureus bacteraemia at two District General Hospitals: 1) adequate and timely removal of the source of bacteraemia, 2) echocardiography to exclude endocarditis, 3) repeat blood culture to prove clearance of bacteraemia, 4) adequate duration and choice of antibiotics and 5) documentation of bacteraemia in the discharge summary. After an initial review revealed several areas for improvement, we instituted five Plan-Do-Study-Act learning cycles which involved: teaching microbiology trainees and junior doctors, improving clinical liaison and communication between the microbiology team and clinicians, as well as a clinical review of patients by the microbiology team where appropriate. The post-intervention review evaluated 24 patients with S. aureus bacteraemia between November 2012 and May 2013. The proportion of patients undergoing an echocardiogram improved from 49% to 88%. Another marked improvement was seen in the timely obtaining of clearance blood cultures, with 88% of patients having clearance blood cultures within the 2-4 day window, compared to 56% pre-intervention. 70% of patients with uncomplicated S. aureus bacteraemia received an appropriate antibiotic course post-intervention, compared with 59% pre-intervention. Documentation of the S. aureus bacteraemia in the discharge summary improved from 65% to 75%. The support of the entire microbiology team was pivotal in the successful outcome of the quality improvement project.

Project description:Rapid determination of antimicrobial susceptibility/resistance is an important factor in selecting an appropriate antimicrobial treatment and eradicating infections promptly. Conventional antimicrobial susceptibility tests (ASTs) are very time consuming. Thus, we developed a liquid chromatography-mass spectrometry (LC-MS/MS) method for rapidly determining the resistance of Staphylococcus aureus to penicillin-G in an animal-infection model. This technique will be able to detect those resistant strains whose resistance mechanism specifically controlled by penicillinase. The resistance status of S. aureus against penicillin-G was determined by conventional AST. Cultured S. aureus cells were inoculated to chicken for developing bacteraemia. The solution of penicillin-G was intravenously administered (10 mg/kg b.w.) to chickens just after infection detection. Blood samples were collected at different intervals after drug administration. The concentration of active penicillin-G and its metabolites were determined from the bacteria-free blood supernatant by utilizing the LC-MS/MS method. Evidence of infection in chicken was observed within 5 h of bacterial inoculation. The penicillinase enzyme generated by S. aureus transforms the active penicillin-G to an inactive metabolite by hydrolysis, which is evident by the mass shift from 335.10600 to 353.11579 Da as quantified using liquid chromatography quadrupole time-of-flight mass spectrometry (LC/Q-TOF/MS). The signal intensity of inactive/hydrolysed penicillin-G is several-fold greater than that of the active penicillin-G in the blood sample of chicken infected with resistant strain and treated with penicillin-G. The antimicrobial resistance index (ARI) value of resistant S. aureus strain was more than 1, demonstrating the penicillin-G-resistance pattern of that strain. This method is able to determine the extent of ?-lactam antimicrobial resistance within 1.5 h from the patient's blood and is complementary with those existing AST methods which are usually practicing in the evaluation of ?-lactam antibiotic resistance.

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Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia.

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Extensive re-modelling of the cell wall during the development of <i>Staphylococcus aureus</i> bacteraemia.

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Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia.

Publications

Extensive re-modelling of the cell wall during the development of &lt;i&gt;Staphylococcus aureus&lt;/i&gt; bacteraemia.

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OmicsDI is part of the ELIXIR infrastructure

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Extensive re-modelling of the cell wall during the development of <i>Staphylococcus aureus</i> bacteraemia.