A guide to Stenotrophomonas maltophilia virulence capabilities, as we currently understand them

Bhaumik, Radhika; Aungkur, Nabiha Zumana; Anderson, Gregory G.

doi:10.3389/fcimb.2023.1322853

Cited by 5 publications

(1 citation statement)

References 149 publications

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“…S. maltophilia infections are often difficult to treat due to the multi-drug-resistant nature of associated strains ( 13 – 15 ). To survive in its various niches, S. maltophilia utilizes biofilm formation and a range of surface and secreted factors, including flagella, siderophore, and enzymes secreted by a type II secretion system ( 16 – 26 ).…”

Section: Introductionmentioning

confidence: 99%

Bactericidal effectors of the Stenotrophomonas maltophilia type IV secretion system: functional definition of the nuclease TfdA and structural determination of TfcB

Cobe,

Dey,

Minasov

et al. 2024

mBio

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Stenotrophomonas maltophilia expresses a type IV protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria and does so partly by secreting the effector TfcB. Here, we report the structure of TfcB, comprising an N-terminal domain similar to the catalytic domain of glycosyl hydrolase (GH-19) chitinases and a C-terminal domain for recognition and translocation by the T4SS. Utilizing a two-hybrid assay to measure effector interactions with the T4SS coupling protein VirD4, we documented the existence of five more T4SS substrates. One of these was protein 20845, an annotated nuclease. A S. maltophilia mutant lacking the gene for 20845 was impaired for killing Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa . Moreover, the cloned 20845 gene conferred robust toxicity, with the recombinant E. coli being rescued when 20845 was co-expressed with its cognate immunity protein. The 20845 effector was an 899 amino-acid protein, comprised of a GHH-nuclease domain in its N-terminus, a large central region of indeterminant function, and a C-terminus for secretion. Engineered variants of the 20845 gene that had mutations in the predicted catalytic site did not impede E. coli , indicating that the antibacterial effect of 20845 involves its nuclease activity. Using flow cytometry with DNA staining, we determined that 20845, but not its mutant variants, confers a loss in DNA content of target bacteria. Database searches revealed that uncharacterized homologs of 20845 occur within a range of bacteria. These data indicate that the S. maltophilia T4SS promotes interbacterial competition through the action of multiple toxic effectors, including a potent, novel DNase. IMPORTANCE Stenotrophomonas maltophilia is a multi-drug-resistant, Gram-negative bacterium that is an emerging pathogen of humans. Patients with cystic fibrosis are particularly susceptible to S. maltophilia infection. In hospital water systems and various types of infections, S. maltophilia co-exists with other bacteria, including other pathogens such as Pseudomonas aeruginosa . We previously demonstrated that S. maltophilia has a functional VirB/D4 type VI protein secretion system (T4SS) that promotes contact-dependent killing of other bacteria. Since most work on antibacterial systems involves the type VI secretion system, this observation remains noteworthy. Moreover, S. maltophilia currently stands alone as a model for a human pathogen expressing an antibacterial T4SS. Using biochemical, genetic, and cell biological approaches, we now report both the discovery of a novel antibacterial nuclease (TfdA) and the first structural determination of a bactericidal T4SS effector (TfcB).

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Section: Introductionmentioning

confidence: 99%

Bactericidal effectors of the Stenotrophomonas maltophilia type IV secretion system: functional definition of the nuclease TfdA and structural determination of TfcB

Cobe,

Dey,

Minasov

et al. 2024

mBio

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Characterization and genomic analysis of phage vB_SmaP_c9-N, a novel Stenotrophomonas maltophilia podophage with antibiofilm activity

Xi,

Zhou,

et al. 2024

Arch Virol

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Evaluation of clinical outcomes and risk factors associated with mortality in patients with Stenotrophomonas maltophilia bloodstream infection: a multicenter study

Gezer,

Tayşi,

Tarakçı

et al. 2024

BMC Infect Dis

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Background Stenotrophomonas maltophilia , a pathogen that colonizes medical equipment and causes nosocomial infections due to its ability to form biofilms, has high mortality rates. This study investigated the risk factors related to mortality in patients who were diagnosed with S. maltophilia bacteremia. Methods It is a multi-center, retrospective ad observational cohort study. The demographic characteristics, clinical findings, microbiological data, and risk factors for patients were obtained from the medical records of patients at ten different hospitals between January 1, 2018, and June 30, 2023. Results The study included a total of 321 patients. The observed thirty-day mortality rate was 46.1%. A central venous catheter (CVC) was present in 276 patients (86%), and in 66 of these patients (23.9%) the CVC was removed. While only 18 patients (5.6%) received appropriate empirical antibiotics, 242 (75.4%) patients received appropriate antibiotics according to antimicrobial susceptibility test (AST) results and treatment revisions. Multivariate analysis revealed that advanced age (hazard ratio [HR] = 1.02; 95% confidence interval [CI]: 1.00– 1.03), appropriate antibiotic treatment (HR = 0.35; 95% CI: 0.23–0.52), and removal of central venous catheters (HR = 0.31; 95% CI: 0.16–0.60) were significantly related to reduced mortality. Conclusions S. maltophilia is a significant pathogen, and to reduce its high mortality rate, removal of the CVC and switching to appropriate antibiotics should be performed as soon as possible.

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A guide to Stenotrophomonas maltophilia virulence capabilities, as we currently understand them

Cited by 5 publications

References 149 publications

Bactericidal effectors of the Stenotrophomonas maltophilia type IV secretion system: functional definition of the nuclease TfdA and structural determination of TfcB

Bactericidal effectors of the Stenotrophomonas maltophilia type IV secretion system: functional definition of the nuclease TfdA and structural determination of TfcB

Characterization and genomic analysis of phage vB_SmaP_c9-N, a novel Stenotrophomonas maltophilia podophage with antibiofilm activity

Evaluation of clinical outcomes and risk factors associated with mortality in patients with Stenotrophomonas maltophilia bloodstream infection: a multicenter study

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