Stenotrophomonas muris-first discovered as a potential human pathogen with strong virulence and antibiotic resistance, associated with bloodstream infections.

Abstract

For the first time, Stenotrophomonas muris, whose pathogenic potential for humans has never been reported previously, has been identified to be associated with human infections. 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 the patient's bloodstream infection) was more virulent than both S8 (S. muris no. 8, isolated from the patient's sputum) and S1 (Stenotrophomonas maltophilia type strain ATCC13637). Candidate genes that 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 infected host cells (THP-1 cells) showed that 13 candidate genes involved in host response to hypoxia (HILPDA, FOXH1, ANGPTL4, SLC2A1, HK2, ADM, CXCR4, BNIP3, PLAT, PLOD2, STC2, STC1, and AK4) were preferentially upregulated by the more virulent strain S9 over the less virulent S8. Two downregulated genes (SLC26A11 and SLC8A1) involved in monoatomic ion transport and the calcium signaling pathway may also need special attention, as they may be involved in pathogenesis. Antibiotic susceptibility testing indicated that strains S8 and S9 demonstrated high resistance to colistin and polymyxin B, with MIC values surpassing clinical breakpoints. For ceftazidime (a cephalosporin) and levofloxacin (a fluoroquinolone), MIC values were elevated in S8/S9 compared to S1 but remained within the susceptible range (ceftazidime: S8 and S9; levofloxacin: S8) or intermediate category (levofloxacin: S9). Because of the above differences in virulence properties and antibiotic susceptibility, it is critical that S. muris be distinguished from S. maltophilia in a 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.

Importance: Stenotrophomonas muris was first discovered as a potential human pathogen. Since it shares 99.72% similarity of the 16S rRNA to Stenotrophomonas maltophilia, conventional diagnostic methods usually classify it as S. maltophilia clinically. However, the two human pathogens should be distinguished. The reason is that they have different virulence and different drug susceptibilities, which result in different administrations of drugs to treat their infections. To better distinguish these two pathogens and treat infections of S. muris, we investigated the virulence genes, the host response of S. muris infections, and susceptibility of S. muris to different drugs. The results we show in this paper will guide researchers to identify virulence genes, diagnostic biomarkers, and targets to develop treatment strategies for S. muris infections.