Deconstructing the Chlamydial Cell Wall

Klöckner, Anna; Bühl, Henrike; Viollier, Patrick H.; Henrichfreise, Beate

doi:10.1007/82_2016_34

Cited by 12 publications

(26 citation statements)

References 168 publications

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“…Waddlia (Klockner et al, 2018) supports the conservation of the cytosolic pathway responsible for lipid II biosynthesis.…”

Section: The Recent Discovery Of Pg Fragments Chlamydia-infected Cellmentioning

confidence: 73%

“…Until recently, there was no formal evidence of the presence of PG in intracellular Chlamydiae despite their susceptibility for beta‐lactams, becoming the presence of an intact lipid II route enigmatic (Henrichfreise et al, ). The recent discovery of PG fragments Chlamydia ‐infected cells and other lineages of Chlamydia ‐related bacteria like Protochlamydia and Waddlia (Klockner et al, ) supports the conservation of the cytosolic pathway responsible for lipid II biosynthesis.…”

Section: Gain and Loss Of Pg Enzymes In Intracellular Pathogens: Oblimentioning

confidence: 88%

“…Only one member of this protein family, a DacC homologue, is identified (Jacquier, Viollier, & Greub, ). Many cell division proteins, like the tubulin homologue FtsZ, are also missing in Chlamydiales with a division process that is orchestrated by the actin homologue MreB and its interactors RodZ and the LysM‐domain‐containing protein AmiA (NlpD), this latter with dual amidase and carboxypeptidase activities (Jacquier, Frandi, Viollier, & Greub, ; Jacquier, Viollier, et al, ; Klockner et al, , ). Such reduced number of periplasmic PG hydrolases is a hallmark of obligate intracellular pathogens (Otten et al, ) and endosymbionts (Wilmes et al, ), contrasting with the more than 35 PG hydrolases known in free‐living bacteria like E. coli (van Heijenoort, ; Vollmer, Joris, et al, ) (Figure b).…”

Section: Gain and Loss Of Pg Enzymes In Intracellular Pathogens: Oblimentioning

confidence: 99%

“…Chlamydiales are Gram-negative bacteria with a biphasic life cycle that alternates between the extracellular and less metabolically active elementary body (EB) and the intracellular and highly active reticulate body (RB) (Klockner, Buhl, Viollier, & Henrichfreise, 2018;Moulder, 1991). The Chlamydiales genome has lost many of the genes encoding periplasmic enzymes involved in PG remodeling as the d,d-carboxypeptidases.…”

Section: G Ain and Loss Of P G Enz Yme S In Intr Acellul Ar Pathog mentioning

confidence: 99%

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Building peptidoglycan inside eukaryotic cells: A view from symbiotic and pathogenic bacteria

Portillo

2020

Molecular Microbiology

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The peptidoglycan (PG), as the exoskeleton of most prokaryotes, maintains a defined shape and ensures cell integrity against the high internal turgor pressure. These important roles have attracted researchers to target PG metabolism in order to control bacterial infections. Most studies, however, have been performed in bacteria grown under laboratory conditions, leading to only a partial view on how the PG is synthetized in natural environments. As a case in point, PG metabolism and its regulation remain poorly understood in symbiotic and pathogenic bacteria living inside eukaryotic cells. This review focuses on the PG metabolism of intracellular bacteria, emphasizing the necessity of more in vivo studies involving the analysis of enzymes produced in the intracellular niche and the isolation of PG from bacteria residing within eukaryotic cells. The review also points to persistent infections caused by some intracellular bacterial pathogens and the extent at which the PG could contribute to establish such physiological state. Based on recent evidences, I speculate on the idea that certain structural features of the PG may facilitate attenuation of intracellular growth. Lastly, I discuss recent findings in endosymbionts supporting a cooperation between host and bacterial enzymes to assemble a mature PG.

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“…Waddlia (Klockner et al, 2018) supports the conservation of the cytosolic pathway responsible for lipid II biosynthesis.…”

Section: The Recent Discovery Of Pg Fragments Chlamydia-infected Cellmentioning

confidence: 73%

Section: Gain and Loss Of Pg Enzymes In Intracellular Pathogens: Oblimentioning

confidence: 88%

Section: Gain and Loss Of Pg Enzymes In Intracellular Pathogens: Oblimentioning

confidence: 99%

Section: G Ain and Loss Of P G Enz Yme S In Intr Acellul Ar Pathog mentioning

confidence: 99%

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Building peptidoglycan inside eukaryotic cells: A view from symbiotic and pathogenic bacteria

Portillo

2020

Molecular Microbiology

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“…C. trachomatis infection may cause infertility in female patients and eye damage, in addition to lung infections(13). Antibiotics, such as -lactam antibiotics, are a common way to treat Chlamydia infection, but the chance of recurrence is high(46,47). Current vaccine development efforts are underway but multiple challenges remain(48).…”

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confidence: 99%

Developing Cyclic Peptomers as Broad-Spectrum Gram negative Bacterial Type III Secretion System Inhibitors

Lam

Lau

Lentz

et al. 2020

Preprint

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Antibiotic resistant bacteria are an emerging global health threat. New antimicrobials are urgently needed. The injectisome type III secretion system (T3SS), required by dozens of Gram-negative bacteria for virulence but largely absent from non-pathogenic bacteria, is an attractive antimicrobial target. We previously identified synthetic cyclic peptomers, inspired by the natural product phepropeptin D, that inhibit protein secretion through the Yersinia Ysc and Pseudomonas aeruginosa Psc T3SSs, but do not inhibit bacterial growth. Here we describe identification of an isomer, 4EpDN, that is two-fold more potent (IC50 4 mM) than its parental compound. Furthermore, 4EpDN inhibited the Yersinia Ysa and the Salmonella SPI-1 T3SSs, suggesting that this cyclic peptomer has broad efficacy against evolutionarily distant injectisome T3SSs. Indeed, 4EpDN strongly inhibited intracellular growth of Chlamydia trachomatis in HeLa cells, which requires the T3SS. 4EpDN did not inhibit the unrelated Twin arginine translocation (Tat) system, nor did it impact T3SS gene transcription. Moreover, although the injectisome and flagellar T3SSs are evolutionarily and structurally related, the 4EpDN cyclic peptomer did not inhibit secretion of substrates through the Salmonella flagellar T3SS, indicating that cyclic peptomers broadly but specifically target the injestisome T3SS. 4EpDN reduced the number of T3SS basal bodies detected on the surface of Y. enterocolitica, as visualized using a fluorescent derivative of YscD, an inner membrane ring with low homology to flagellar protein FliG. Collectively, these data suggest that cyclic peptomers specifically inhibit the injectisome T3SS from a variety of Gram-negative bacteria, possibly by preventing complete T3SS assembly.

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Medicinal Chemistry of β‐Lactam Antibiotics

Testero

Llarrull

Fisher

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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The β‐lactam class of antibacterials is a cornerstone of human health. For nearly eight decades, their unparalleled clinical efficacy and clinical safety have made the β‐lactam class preeminent in the treatment of bacterial infection. The relatively brief period in human history during which the β‐lactams have exerted this benefit is a period characterized by continuous medicinal chemistry innovation, seen visibly in the progression from the penicillins to the complex ensemble of β‐lactams (now including also cephalosporins, monobactams, and carbapenems) used in the clinic. The key force behind this innovation is the progressive evolution by bacteria of resistance mechanisms. Today, highly resistant bacteria challenge the way medicinal chemists contemplate the creative alteration of β‐lactam structures, the way the pharmaceutical industry develops β‐lactams (and other antibacterial) structures, and the way the medical community uses antibacterials. This article gives a concise summary of the history of the β‐lactams. Its emphasis is recent structural innovation with respect to the β‐lactams, and with respect to structurally related classes that act to preserve the clinical activity of the β‐lactams through inhibition of bacterial β‐lactam‐hydrolyzing, and thus β‐lactam‐deactivating, enzymes. We integrate these chemistry advances with new biological discoveries with respect to the bactericidal mechanism of the β‐lactams and with respect to bacterial resistance mechanisms. The combination of these perspectives is a foundational perspective to guide the medicinal chemistry future of the β‐lactams.

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Deconstructing the Chlamydial Cell Wall

Cited by 12 publications

References 168 publications

Building peptidoglycan inside eukaryotic cells: A view from symbiotic and pathogenic bacteria

Building peptidoglycan inside eukaryotic cells: A view from symbiotic and pathogenic bacteria

Developing Cyclic Peptomers as Broad-Spectrum Gram negative Bacterial Type III Secretion System Inhibitors

Medicinal Chemistry of β‐Lactam Antibiotics

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