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

Abstract

For the first time, Stenotrophomonas muris (S. muris) has been identified to be a likely human pathogen 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 by SYTOX Green staining, lactate dehydrogenase (LDH) release and Galleria mellonella survival assay and a mouse model of infection that S9 (S. muris no.9, isolated from the patient's bloodstream infection) was more virulent than both S8 (S. muris no.8, isolated from the patient's sputum) and S1 (S. maltophilia type strain ATCC13637), where S8 and S9 were subsequently identified as S. muris by whole genome sequencing analysis. Based on the GO and KEGG databases, part of the candidate genes which possibly encode higher virulence of S9 were identified, including virB6, dcm, hlyD, group_374, group_3203, group_3063, group_832, group_962, group_2016, group_2745, group_3011, group_849, group_1035 and group_1019. Transcriptome analysis of host cells (THP-1 cells) infected by S8 and S9 was performed to investigate the host responses to S. muris infections. It was found that the differentially expressed genes of the infected host cells (group S9 with strong virulence vs group S8 with weak virulence) showed that 12 candidate genes involved in ion transport function and calcium signaling pathway are down-regulated and needed special attention. Susceptibility testing indicates that the treatment regimen of S. muris infections needs to be different from that of S. maltophilia, further demonstrating the necessity of distinguishing these two pathogens. It is also shown that minocycline could be effective for treatment of infections of S. muris. This work highlights the need to pay more attention to S. muris in clinical setting which could be a human pathogen of high risk, as well as provides the basis for subsequent study on the virulence genes and pathogenic mechanisms of S. muris.