Localization and characterization of a putative cysteine desulfurase in Chlamydia psittaci

Abstract

Chlamydia psittaci is an obligate intracellular pathogen with a biphasic developmental life cycle. It is auxotrophic for a variety of essential metabolites and obtains amino acids from eukaryotic host cells. Chlamydia can develop inside host cells within chlamydial inclusions. A pathway secreting proteins from inclusions into the host cellular cytoplasm is the type III secretion system (T3SS). The T3SS is universal among several Gram-negative bacteria. Here, we show that CPSIT_0959 of C. psittaci is expressed midcycle and secreted into the infected cellular cytoplasm via the T3SS.Recombinant CPSIT_0959 possesses cysteine desulfurase and PLP-binding activity, which removes sulfur from cysteine to produce alanine, and helps chlamydial replication. Our study shows that CPSIT_0959 improve the infectivity of offspring elementary bodies and seems to promote the replication by its product. This phenomenon has inhibited by the PLP-dependent enzymes inhibitor. Moreover, CPSIT_0959 increased expression of Bim and tBid, and decreased the mitochondrial membrane potential of host mitochondria to induce apoptosis in the latecycle for release of offspring. These results demonstrate that CPSIT_0959 has cysteine desulfurase and PLP-binding activity and is likely to contribute to apoptosis of the infected cells via a mitochondria-mediated pathway to improve the infectivity of progeny. K E Y W O R D S cellular localization, Chlamydia psittaci, cysteine desulfurase, mitochondria-mediated pathway, T3SS

Sixteen cases of severe pneumonia caused by Chlamydia psittaci in South China investigated via metagenomic next-generation sequencing

“…psittaci is a Gram-negative obligate intracellular organism and an economically relevant pathogen in poultry and pet birds [16]. They are characterized by a unique biphasic developmental cycle including two forms: the elementary and the reticulated bodies [17]. It adapted to a broad range of hosts, including mammals and avian species [7].…”

The Putative Type III Secreted Chlamydia abortus Virulence-Associated Protein CAB063 Targets Lamin and Induces Apoptosis

“…In agreement with these findings, we identified the chlamydial chaperone DnaK (heat shock protein 70, HSP70) as a prokaryotic target of CAB063. Since HSP70 chaperones are involved in protein folding (Bukau et al, 2000;Maleki et al, 2016) as well as translocation (Ryan and Pfanner, 2001;Stevens et al, 2003), our data provide further evidence for CAB063 to be a type III secreted chlamydial effector protein, as they occur in other Chlamydia species as well (Mojica et al, 2015;da Cunha et al, 2017;Wen et al, 2019). Although CAB063 transcription could not be detected any earlier than 32 hpi and reached its maximum at 44 hpi, CAB063 protein could be found as early as 24 hpi in the chlamydial inclusions and from 36 hpi onward in the nuclear fraction of infected HeLA cell (Forsbach-Birk et al, 2013).…”

The Hypothetical Inclusion Membrane Protein CPSIT_0846 Regulates Mitochondrial-Mediated Host Cell Apoptosis via the ERK/JNK Signaling Pathway

“…generation of EBs is formed, some Chlamydial effector proteins can promote host cell apoptosis, such as CPSIT_0959 in C. psittaci, which helps the release of offspring EBs, and ultimately promotes EBs to infect neighboring host cells Sun et al, 2017;Weber et al, 2017;Wen et al, 2019;Marschall et al, 2020). Whether they are to promote or inhibit host cell apoptosis, all of these are the way that Chlamydia has evolved in order to survive in the host cell.…”

“…Apoptosis is a critical defence mechanism that helps to maintain balance in the immune system and protect hosts against pathogen infection (Naoi et al, 2019). Chlamydia can inhibit apoptosis in host cells during the early stages of infection to ensure their proliferation (Wen et al, 2019). C. trachomatis can activate PDPK1-MYC, enhance the binding of hexase II (HKII) to mitochondria, and thereby resist apoptosis (Al-Zeer et al, 2017).…”