Stenotrophomonas muris- First discovered as an urgent human pathogen with strong virulence associated with bloodstream infections

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Abstract

For the first time, Stenotrophomonas muris ( S. muris ) has been identified to be associated with human infections while studying the virulence of Stenotrophomonas maltophilia ( S. maltophilia ) clinical isolates. Previously, S. muris was only isolated from the intestines of mice but its pathogenic potential for humans has never been reported. In this work, the phenotype of S. muris virulence, the potential genes that encode higher virulence of S. muris , and host responses to S. muris infection were investigated for the first time. It was found that S9 ( S. muris no.9, isolated from patient’s bloodstream infection) was more virulent than both S8 ( S. muris no.8, isolated from patient’s sputum) and S1 ( S. maltophilia ), where S8 and S9 were subsequently identified as S. muris by whole genome sequencing analysis. Candidate genes which may encode higher virulence of S9 were identified, including virB6, dcm, hlyD , and 14 other genes involved in porphyrin metabolism, pyrimidine metabolism, DNA methylation, two component system, and biofilm formation. Transcriptome analysis of host cells (THP-1 cells) infected by S8 and S9 (S9 with strong virulence over S8 with weak virulence) showed that 12 candidate genes involved in ion transport function and calcium signaling pathway were down-regulated and require special attention. Antibiotic susceptibility testing indicated that compared with S. maltophilia , the S. muris strains, though more susceptible to minocycline, are highly resistant to last resort antibitoics colistin and polymyxin B and are also resistant to cephalosporin and fluoroquinolone. Because of the above differences in virulence properties and antibiotic susceptibility, it is critical that S. muris be distinguished from S. maltophilia in clinical setting for improved care. This work provides the basis for future studies on pathogenic mechanisms of S. muris and for developing improved treatment in the future.

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