Stenotrophomonas maltophilia virulence: a current view

Abstract

Stenotrophomonas maltophilia is an opportunistic pathogen intrinsically resistant to multiple and broad-spectrum antibiotics. Although the bacterium is considered a low-virulence pathogen, it can cause various severe diseases and contributes significantly to the pathogenesis of multibacterial infections. During the COVID-19 pandemic, S. maltophilia has been recognized as one of the most common causative agents of respiratory co-infections and bacteremia in critically ill COVID-19 patients. The high ability to adapt to unfavorable environments and new habitat niches, as well as the sophisticated switching of metabolic pathways, are unique mechanisms that attract the attention of clinical researchers and experts studying the fundamental basis of virulence. In this review, we have summarized the current knowledge on the molecular aspects of S. maltophilia virulence and putative virulence factors, partially touched on interspecific bacterial interactions and iron uptake systems in the context of virulence, and have not addressed antibiotic resistance.

Keywords: Stenotrophomonas maltophilia; biofilms; iron uptake systems; quorum sensing; virulence factors.

Figure 1

Virulence and putative virulence factors in Stenotrophomonas maltophilia. Surface cell-associated structures include lipopolysaccharides (LPS), type IV pili (T4P), flagella, fimbriae (SMF-1), and non-pilus adhesins (not shown). Extracellular enzymes are secreted through type I, II, IV, V, and VI secretion systems. Small molecules efflux to the environment via the diffusible signal factor (DSF) and outer membrane vesicles (OMV). S. maltophilia produces extracellular polymeric substances and forms a self-secreted polymeric matrix, biofilms, consisting of exopolysaccharides (EPS), DNA, and proteins. The intracellular c-di-GMP level contributes to numerous virulence factors (see the text for details). Different types of efflux pumps revealed in S. maltophilia are shown on the right. The pumps involved in virulence are marked in bold.

Figure 2

Iron acquisition and iron export systems in Stenotrophomonas maltophilia. IM, inner membrane; P, periplasm; PG; peptidoglycan; OM, outer membrane. AmpI, the inner membrane iron exporter; EFC, exogenous ferric citrate; ESP, an exogenous siderophore (siderophores produced by other bacteria, e.g., Pseudomonas aeruginosa); FciA, the outer membrane receptor for ferric citrate uptake; FciT (inner membrane protein) and FciC (cytoplasmic protein), putative proteins for citrate-mediated iron acquisition; FCS, the ferric citrate siderophore complex; FeoA, a cytoplasmic protein; FeoABI, the inner membrane transporter system of ferric citrate; FepA, the ferri-siderophore uptake system; FepB, a protein delivering ferric siderophore from the periplasm; FepCDG, the inner membrane transporter system for ferric siderophores; HemA, the TonB-dependent outer membrane receptor for hemin; HM, hemin; HmuT, a hemin-transporting protein; HmuUV, the inner membrane hemin transporter; IMSE, the inner membrane siderophore exporters (EntS for enterobactin, SmeY, SbiA, and SmeD for stenobactin); SmeF, the outer membrane exporter for siderophore; SP, S. maltophilia siderophore (stenobactin or enterobactin).