Salmonella Intracellular Lifestyles and Their Impact on Host-to-Host Transmission

Abstract

More than a century ago, infections by were already associated with foodborne enteric diseases with high morbidity in humans and cattle. Intestinal inflammation and diarrhea are hallmarks of infections caused by nontyphoidal serovars, and these pathologies facilitate pathogen transmission to the environment. In those early times, physicians and microbiologists also realized that typhoid and paratyphoid fever caused by some serovars could be transmitted by "carriers," individuals outwardly healthy or at most suffering from some minor chronic complaint. In his pioneering study of the nontyphoidal serovar Typhimurium in 1967, Takeuchi published the first images of intracellular bacteria enclosed by membrane-bound vacuoles in the initial stages of the intestinal epithelium penetration. These compartments, called-containing vacuoles, are highly dynamic phagosomes with differing biogenesis depending on the host cell type. Single-cell studies involving real-time imaging and gene expression profiling, together with new approaches based on genetic reporters sensitive to growth rate, have uncovered unprecedented heterogeneous responses in intracellular bacteria. Subpopulations of intracellular bacteria displaying fast, reduced, or no growth, as well as cytosolic and intravacuolar bacteria, have been reported in both and infection models. Recent investigations, most of them focused on the serovar Typhimurium, point to the selection of persisting bacteria inside macrophages or following an autophagy attack in fibroblasts. Here, we discuss these heterogeneous intracellular lifestyles and speculate on how these disparate behaviors may impact host-to-host transmissibility of serovars.

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“…Here, we have probed bacterial host cell binding and invasion mechanisms, but this approach is in fact much more versatile than that. Barcoded consortium infections will also permit the tracing of competing strains over the subsequent stages of host cell colonization, i.e., intracellular survival, trafficking, replication, and egress (46, 47).…”

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“…S. Typhimurium causes a natural, systemic, murine infection by multiplying within phagosomes of cells of the monocyte lineage [16]. Within phagosomes, S. Typhimurium is exposed to particularly harsh conditions, including various AMPs, proteases, lysozyme, low pH, and limited nutrients [17,18]. AMPs and magnesium limitation specifically compromise the LPS surface O-antigen polysaccharide in the outer membrane, increasing bacterial susceptibility to other host insults [15,19].…”

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“…112 However, certain intracellular bacterial pathogens, such as Mycobacterium tuberculosis, 113,114 Salmonella enterica, 115 and Klebsiella pneumoniae, 116 develop various defence mechanisms to escape the phagocytosis pathways or remain viable in the phagolysosomes, which is the case for infectious diseases, such as tuberculosis, 117 listeriosis, 118 and salmonellosis. 119 Recent research demonstrated that Klebsiella pneumoniae can promote the activation of Akt to arrest phagosome maturation, avoiding fusion into lysosomes, thus creating a Klebsiella-containing vacuole to survival intracellularly (Fig. 7B, route 1).…”

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“…might either be taken up by circulating phagocytes or invade into adjacent enterocytes basolaterally. Inside host cells, Salmonella as a facultative intracellular bacterial pathogen creates its replicative niche by residing within Salmonella ‐containing vacuoles to protect itself from host defences (for detailed reviews of Salmonella pathogenesis, see,e.g., Ohl & Miller, ; Pinaud et al, ; Pucciarelli & Garcia‐Del Portillo, ).…”

“…Additionally, YopM antagonises inflammasome formation either by direct interaction with caspase-1 or indirectly by targeting the regulatory protein IQGAP1 (IQ motif-containing GTPase-activating protein 1; Chung et al, 2014;LaRock & Cookson, 2012). Apart from residing in the cytosol, YopM was found to enter the nucleus, probably by vesicle-associated transport (Benabdillah, Mota, Lutzelschwab, Demoinet, & Cornelis, 2004;Skrzypek, Cowan, & Straley, 1998), whereas nuclear export depends Inside host cells, Salmonella as a facultative intracellular bacterial pathogen creates its replicative niche by residing within Salmonellacontaining vacuoles to protect itself from host defences (for detailed reviews of Salmonella pathogenesis, see,e.g., Ohl & Miller, 2001;Pinaud et al, 2018;Pucciarelli & Garcia-Del Portillo, 2017). (Rao et al, 2017).…”