Chronic Bacterial Pathogens: Mechanisms of Persistence

Abstract

Summary Many bacterial pathogens can cause acute infections that are cleared with onset of adaptive immunity, however a subset of these pathogens can establish persistent, and sometimes lifelong infections. While bacteria causing chronic infections are phylogenetically diverse, they share common features in their interactions with the host that enable a protracted period of colonization. This chapter will compare the persistence strategies of two chronic pathogens from the Proteobacteria, Brucella abortus, and Salmonella enterica serovar Typhi (S. Typhi) to consider how these two pathogens, which are very different at the genomic level, can utilize common strategies to evade immune clearance to cause chronic intracellular infections of the mononuclear phagocyte system.

Omp25‐dependent engagement of SLAMF1 byBrucella abortusin dendritic cells limits acute inflammation and favours bacterial persistence in vivo

“…During the acute phase of infection just after entry in the host, activated immune cells are recruited in lymphoid organs. Later on, during chronic infection, infected cells change their metabolism and become anti‐inflammatory (Byndloss & Tsolis, ). When the Omp25/SLAMF1 axis is missing, immune cells might not switch their metabolism to an anti‐inflammatory phenotype and thus continue to produce inflammatory cytokines leading to the killing of infected cells.…”

“…Bacteria have therefore developed efficient strategies to evade immune system recognition and elimination (Brodsky & Medzhitov, ; Sansonetti & Di Santo, ). Targeting the signalling triggered by pattern recognition receptors in antigen‐presenting cells is one of them (Byndloss & Tsolis, ). However, little is known about other cell surface host‐bacteria‐interacting factors that contribute to promoting chronicity, and a firm demonstration of a direct link between such interaction and progress towards chronic infection is still under scrutiny.…”

Evaluating New Compounds to Treat Burkholderia pseudomallei Infections

“…The ability of B. pseudomallei to generate persistent populations is thought to be a major contributor to latent infections which can recrudesce when the immune system is compromised (Chaowagul et al, 1993 ). Bacterial persistence is well documented to be associated with chronic infections and infection relapse (Zhang, 2014 ; Byndloss and Tsolis, 2016 ). Persistence is a mechanism by which a portion of an antibiotic susceptible population enters a dormant-like state, rendering antibiotics ineffective.…”

Brucella Hijacks Host-Mediated Palmitoylation To Stabilize and Localize PrpA to the Plasma Membrane

“…These virulence factors need to be stabilized and localized in specific compartments of the cell to find and modulate their targets (9). Brucella is an intracellular pathogen with the capacity to invade and replicate in many cell types of the infected host and to establish a persistent infection (3,4). To achieve this, the bacterium has the capacity to translocate to the host cells a plethora of proteins that alter either the normal trafficking of the intracellular bacteria or the immune response triggered by the infection (3,10).…”

“…Brucella abortus is a chronic pathogen that has evolved a wide variety of immune evasion strategies in order to persist in the context of a robust immune response. These strategies include downregulating the activation of certain pathogen-associated molecular patterns (PAMPs), synthesis of structural components with low proinflammatory activities, and alteration of the normal course of the adaptive immune response (3,4). One example of the last type of modulation is the one triggered by PrpA (for proline racemase protein A), a protein of Brucella that our group has identified and characterized as a polyclonal B-cell mitogen involved in the establishment of the chronic phase of the infectious process in mice (5).…”