Type IVB Secretion by Intracellular Pathogens

Abstract

A growing number of pathogens are being found to possess specialized secretion systems which they use in various ways to subvert host defenses. One class, called type IV, are defined as having homology to the conjugal transfer systems of naturally occurring plasmids. It has been proposed that pathogens with type IV secretion systems have acquired and adapted the conjugal transfer systems of plasmids and now use them to export toxins. Several well-characterized intracellular pathogens, including Legionella pneumophila, Coxiella burnetii, Brucella abortus, and Rickettsia prowazekii, contain type IV systems which are known or suspected to be of critical importance in their ability to cause disease. Specifically, these systems are believed to be the key factors determining intracellular fate, and thus the ability to replicate and cause disease.

Coupling Factors in Macromolecular Type-IV Secretion Machineries

“…They bear Walker A (motif I) and B (motif II or DExx box) NTP-binding sequences [88] and may use the energy of Rhizobium etli bacterium; N2-fixation [154] Sinorhizobium meliloti bacterium; N2-fixation [14,15,17] Shigella flexneri plasmid ColIb P9 bacterium; diarrhoea / dysentery [155] Bartonella henselae and tribocorum bacterium; cat scratch disease, bacteremia [156][157][158][159][160] Campylobacter jejuni bacterium; bacterial diarrhoea [161,162] Toxoplasma gondii protozoon; toxoplasmosis (encephalitis) [54] Leishmania donovani protozoon; leishmaniasis [54] Mycobacterium tuberculosis bacterium; tuberculosis [54] Bordetella bronchiseptica bacterium; bronchitis [14,15,17] Enterobacter aerogenes bacterium; nosocomial infections [11] Actinobacillus actinomycetemcomitans bacterium; periodontitis [14,15,17,163,164] Escherichia coli bacterium; diarrhea [11] Caulobacter crescentus bacterium; non-pathogenic [14,15,17] Coxiella burnetii bacterium; acute febrile disease, endocarditis, pneumonitis [165,166] Thiobacillus ferroxidans bacterium; iron oxidation [14,15,17] Wolbachia intracellular symbiont of arthropods; sexual alterations in host [167,168] Ralstonia eutrophantus bacterium; heavy-metal resistance [11,169] Salmonella typhi, typhimurium and enteriditis bacterium; typhus, salmonellosis …”

Coxiella burnetii modulates Beclin 1 and Bcl-2, preventing host cell apoptosis to generate a persistent bacterial infection

“…27 Our group has shown that Cb survives and replicates in a large replicative vacuole (C. burnetii-replicative vacuoles (CRVs)) with clear autophagic features. 28 Besides, autophagy induction before infection, as well as the overexpression of proteins involved in this pathway (i.e.…”

Autophagy and Inflammatory Cell Death, Partners of Innate Immunity

“…22 Consequently, inflammasomes assemble and activate caspase 1 by a mechanism that requires the JNK signal transduction pathway. When the contamination is scant, macrophages elevate autophagy, a membrane trafficking pathway that captures the pathogen within membranes derived from the early secretory pathway for delivery to degradative lysosomes.…”