Bordetella Type III Secretion Injectosome and Effector Proteins

Abstract

Pertussis, also known as whooping cough, is a resurging acute respiratory disease of humans primarily caused by the Gram-negative coccobacilli Bordetella pertussis, and less commonly by the human-adapted lineage of B. parapertussis HU. The ovine-adapted lineage of B. parapertussis OV infects only sheep, while B. bronchiseptica causes chronic and often asymptomatic respiratory infections in a broad range of mammals but rarely in humans. A largely overlapping set of virulence factors inflicts the pathogenicity of these bordetellae. Their genomes also harbor a pathogenicity island, named bsc locus, that encodes components of the type III secretion injectosome, and adjacent btr locus with the type III regulatory proteins. The Bsc injectosome of bordetellae translocates the cytotoxic BteA effector protein, also referred to as BopC, into the cells of the mammalian hosts. While the role of type III secretion activity in the persistent colonization of the lower respiratory tract by B. bronchiseptica is well recognized, the functionality of the type III secretion injectosome in B. pertussis was overlooked for many years due to the adaptation of laboratory-passaged B. pertussis strains. This review highlights the current knowledge of the type III secretion system in the so-called classical Bordetella species, comprising B. pertussis, B. parapertussis, and B. bronchiseptica, and discusses its functional divergence. Comparison with other well-studied bacterial injectosomes, regulation of the type III secretion on the transcriptional and post-transcriptional level, and activities of BteA effector protein and BopN protein, homologous to the type III secretion gatekeepers, are addressed.

Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts

“…In addition, many intracellular bacterial pathogens have evolved to modulate and reprogram host metabolism to generate the nutrients needed to support pathogen proliferation [ 22 , 23 , 24 , 25 ]. A major theme among pathogens that have evolved to modulate cellular biology is the injection of bacterial proteins directly into the host cell through specialized nanosyringes that penetrate eukaryotic membranes and inject pathogenic effector proteins, and these nanosyringes are classified as type III-IX secretions systems [ 26 , 27 , 28 , 29 , 30 , 31 ]. Many host post-translational modifications machineries are targeted by various injected bacterial effectors [ 32 ].…”

Omics Analysis of Blood-Responsive Regulon in Bordetella pertussis Identifies a Novel Essential T3SS Substrate

“…Thus far, only two effector proteins have been described in bordetellae. The BteA effector, also named BopC, is responsible for the cytotoxicity linked to T3SS, but its mechanism of action remains unknown [ 22 , 23 , 24 ]. Interestingly, an amino acid insertion within B. pertussis BteA protein renders this effector less cytotoxic compared to one produced by B. bronchiseptica [ 25 ].…”

Lipid binding by N-terminal motif mediates plasma membrane localization ofBordetellaeffector protein BteA

“…The cytotoxic effector BteA is injected into the host cells by a type III secretion system (T3SS) of classical Bordetella species, B. pertussis and B. bronchiseptica [11].…”

“…The cytotoxic effector BteA is injected into the host cells by a type III secretion system (T3SS) of classical Bordetella species, B. pertussis and B. bronchiseptica [11]. These bacteria colonize the ciliated epithelia of the respiratory tract of diverse mammals and cause respiratory illness with differing symptoms, duration, and severity.…”