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Penicillin kills Chlamydia following the fusion of bacteria with lysosomes and prevents genital inflammatory lesions in C. muridarum-infected mice.

Dumoux, M; Le Gall, SM; Habbeddine, M; Delarbre, C; Hayward, RD; Kanellopoulos-Langevin, C; Verbeke, P; (2013) Penicillin kills Chlamydia following the fusion of bacteria with lysosomes and prevents genital inflammatory lesions in C. muridarum-infected mice. PLoS One , 8 (12) , Article e83511. 10.1371/journal.pone.0083511. Green open access

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Abstract

The obligate intracellular bacterium Chlamydia exists as two distinct forms. Elementary bodies (EBs) are infectious and extra-cellular, whereas reticulate bodies (RBs) replicate within a specialized intracellular compartment termed an 'inclusion'. Alternative persistent intra-cellular forms can be induced in culture by diverse stimuli such as IFNγ or adenosine/EHNA. They do not grow or divide but revive upon withdrawal of the stimulus and are implicated in several widespread human diseases through ill-defined in vivo mechanisms. β-Lactam antibiotics have also been claimed to induce persistence in vitro. The present report shows that upon penicillin G (pG) treatment, inclusions grow as fast as those in infected control cells. After removal of pG, Chlamydia do not revert to RBs. These effects are independent of host cell type, serovar, biovar and species of Chlamydia. Time-course experiments demonstrated that only RBs were susceptible to pG. pG-treated bacteria lost their control over host cell apoptotic pathways and no longer expressed pre-16S rRNA, in contrast to persistent bacteria induced with adenosine/EHNA. Confocal and live-video microscopy showed that bacteria within the inclusion fused with lysosomal compartments in pG-treated cells. That leads to recruitment of cathepsin D as early as 3 h post pG treatment, an event preceding bacterial death by several hours. These data demonstrate that pG treatment of cultured cells infected with Chlamydia results in the degradation of the bacteria. In addition we show that pG is significantly more efficient than doxycycline at preventing genital inflammatory lesions in C. muridarum-C57Bl/6 infected mice. These in vivo results support the physiological relevance of our findings and their potential therapeutic applications.

Type: Article
Title: Penicillin kills Chlamydia following the fusion of bacteria with lysosomes and prevents genital inflammatory lesions in C. muridarum-infected mice.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0083511
Publisher version: https://doi.org/10.1371/journal.pone.0083511
Language: English
Additional information: © 2013 Dumoux et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Animals, Anti-Bacterial Agents, Chlamydia, Chlamydia Infections, Female, Inflammation, Lysosomes, Mice, Penicillin G, Vagina
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1453006
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