Serratia marcescens is an opportunistic human pathogen that represents a growing problem for public health, particularly in hospitalized or immunocompromised patients. However, little is known about factors and mechanisms that contribute to S. marcescens pathogenesis within its host. In this work, we explore the invasion process of this opportunistic pathogen to epithelial cells. We demonstrate that once internalized, Serratia is able not only to persist but also to multiply inside a large membrane-bound compartment. This structure displays autophagic-like features, acquiring LC3 and Rab7, markers described to be recruited throughout the progression of antibacterial autophagy. The majority of the autophagic-like vacuoles in which Serratia resides and proliferates are non-acidic and have no degradative properties, indicating that the bacteria are capable to either delay or prevent fusion with lysosomal compartments, altering the expected progression of autophagosome maturation. In addition, our results demonstrate that Serratia triggers a non-canonical autophagic process before internalization. These findings reveal that S. marcescens is able to manipulate the autophagic traffic, generating a suitable niche for survival and proliferation inside the host cell.
Serratia marcescens strains are ubiquitous bacteria isolated from environmental niches, such as soil, water, and air, and also constitute emergent nosocomial opportunistic pathogens. Among the numerous extracellular factors that S. marcescens is able to produce, the PhlA phospholipase is the only described exoprotein secreted by the flagellar apparatus while simultaneously being a member of the flagellar regulon. To gain insight into the regulatory mechanism that couples PhlA and flagellar expression, we conducted a generalized insertional mutagenesis and screened for PhlA-deficient strains. We found that three independent mutations in the wec cluster, which impaired the assembly of enterobacterial common antigen (ECA), provoked the inhibition of PhlA expression. Swimming and swarming assays showed that in these strains, motility was severely affected. Microscopic examination and flagellin immunodetection demonstrated that a strong defect in flagellum expression was responsible for the reduced motility in the wec mutant strains. Furthermore, we determined that in the ECA-defective strains, the transcriptional cascade that controls flagellar assembly was turned off due to the down-regulation of flhDC expression. These findings provide a new perspective on the physiological role of the ECA, providing evidence that in S. marcescens, its biosynthesis conditions the expression of the flagellar regulon.Serratia marcescens is an opportunistic human pathogen associated with urinary and respiratory tract as well as wound and eye infections, endocarditis, osteomyelitis, meningitis, and septicemia. Immunocompromised people and newborns are the most affected hosts. The incidence of S. marcescens infection has increased over the last years, mainly due to the acquisition of multiple antibiotic resistance (19,20). S. marcescens produces numerous extracellular factors, including hemolysin, esterase, DNase, chloroperoxidase, S-layer, lipases, proteases, chitinases, and siderophohore (21,24,26,27,31,38,44,45). These factors are predicted to play a role in bacterial environmental adaptive capacity, in either nonhost or host environments, contributing to its ambient persistence and to its pathogenic potential. In addition, an extracellular phospholipase named PhlA in Serratia liquefaciens MG1 (recently reclassified as S. marcescens MG1) and PlaA in Serratia sp. strain MK1 has been described previously (16, 48). The phlAB (or plaAS) locus codes for the PhlA (PlaA) phospholipase and for an accessory protein (PhlB/PlaS) that prevents the intracellular phospholipase enzymatic action. Interestingly, it has been shown not only that the phlAB promoter region displays homology to class III promoters of the flagellar transcriptional cascade controlled by the FliA sigma factor (15) but also that PhlA secretion depends on the integrity of the type III flagellar system export apparatus (15-17).The flagellar structure has its dedicated type III protein export embedded apparatus that translocates proteins involved in the self-assembly process an...
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