Unique Mode of Cell Division by the Mycobacterial Genetic Resister Clones Emerging <italic toggle="yes">De Novo</italic> from the Antibiotic-Surviving Population

ABSTRACT The emergence of antibiotic genetic resisters of pathogenic bacteria poses a major public health challenge. The mechanism by which bacterial antibiotic genetic resister clones formed de novo multiply and establish a resister population remained unknown. Here, we delineated the unique mode o...

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Autores principales:	Kishor Jakkala, Avraneel Paul, Atul Pradhan, Rashmi Ravindran Nair, Deepti Sharan, Sharmada Swaminath, Parthasarathi Ajitkumar
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	antibiotic resisters hydroxyl radical multinucleation multiseptation multiple constriction multiple division Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c0074690c9f24c92929f11a46150eaae
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spelling	oai:doaj.org-article:c0074690c9f24c92929f11a46150eaae2021-11-15T15:31:13ZUnique Mode of Cell Division by the Mycobacterial Genetic Resister Clones Emerging <italic toggle="yes">De Novo</italic> from the Antibiotic-Surviving Population10.1128/mSphere.00994-202379-5042https://doaj.org/article/c0074690c9f24c92929f11a46150eaae2020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00994-20https://doaj.org/toc/2379-5042ABSTRACT The emergence of antibiotic genetic resisters of pathogenic bacteria poses a major public health challenge. The mechanism by which bacterial antibiotic genetic resister clones formed de novo multiply and establish a resister population remained unknown. Here, we delineated the unique mode of cell division of the antibiotic genetic resisters of Mycobacterium smegmatis and Mycobacterium tuberculosis formed de novo from the population surviving in the presence of bactericidal concentrations of rifampicin or moxifloxacin. The cells in the rifampicin/moxifloxacin-surviving population generated elevated levels of hydroxyl radical-inflicting mutations. The genetic mutants selected against rifampicin/moxifloxacin became multinucleated and multiseptated and developed multiple constrictions. These cells stochastically divided multiple times, producing sister-daughter cells phenomenally higher in number than what could be expected from their generation time. This caused an abrupt, unexpectedly high increase in the rifampicin/moxifloxacin resister colonies. This unique cell division behavior was not shown by the rifampicin resisters formed naturally in the actively growing cultures. We could detect such abrupt increases in the antibiotic resisters in others’ and our earlier data on the antibiotic-exposed laboratory/clinical M. tuberculosis strains, M. smegmatis and other bacteria in in vitro cultures, infected macrophages/animals, and tuberculosis patients. However, it went unnoticed/unreported in all those studies. This phenomenon occurring in diverse bacteria surviving against different antibiotics revealed the broad significance of the present study. We speculate that the antibiotic-resistant bacillary clones, which emerge in patients with diverse bacterial infections, might be using the same mechanism to establish an antibiotic resister population quickly in the continued presence of antibiotics. IMPORTANCE The bacterial pathogens that are tolerant to antibiotics and survive in the continued presence of antibiotics have the chance to acquire genetically resistant mutations against the antibiotics and emerge de novo as antibiotic resisters. Once the antibiotic resister clone has emerged, often with compromise on growth characteristics, for the protection of the species, it is important to establish an antibiotic-resistant population quickly in the continued presence of the antibiotic. In this regard, the present study has unraveled multinucleation and multiseptation followed by multiple constrictions as the cellular processes used by the bacteria for quick multiplication to establish antibiotic-resistant populations. The study also points out the same phenomenon occurring in other bacterial systems investigated in our laboratory and others’ laboratories. Identification of these specific cellular events involved in quick multiplication offers additional cellular processes that can be targeted in combination with the existing antibiotics’ targets to preempt the emergence of antibiotic-resistant bacterial strains.Kishor JakkalaAvraneel PaulAtul PradhanRashmi Ravindran NairDeepti SharanSharmada SwaminathParthasarathi AjitkumarAmerican Society for Microbiologyarticleantibiotic resistershydroxyl radicalmultinucleationmultiseptationmultiple constrictionmultiple divisionMicrobiologyQR1-502ENmSphere, Vol 5, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotic resisters hydroxyl radical multinucleation multiseptation multiple constriction multiple division Microbiology QR1-502
spellingShingle	antibiotic resisters hydroxyl radical multinucleation multiseptation multiple constriction multiple division Microbiology QR1-502 Kishor Jakkala Avraneel Paul Atul Pradhan Rashmi Ravindran Nair Deepti Sharan Sharmada Swaminath Parthasarathi Ajitkumar Unique Mode of Cell Division by the Mycobacterial Genetic Resister Clones Emerging <italic toggle="yes">De Novo</italic> from the Antibiotic-Surviving Population
description	ABSTRACT The emergence of antibiotic genetic resisters of pathogenic bacteria poses a major public health challenge. The mechanism by which bacterial antibiotic genetic resister clones formed de novo multiply and establish a resister population remained unknown. Here, we delineated the unique mode of cell division of the antibiotic genetic resisters of Mycobacterium smegmatis and Mycobacterium tuberculosis formed de novo from the population surviving in the presence of bactericidal concentrations of rifampicin or moxifloxacin. The cells in the rifampicin/moxifloxacin-surviving population generated elevated levels of hydroxyl radical-inflicting mutations. The genetic mutants selected against rifampicin/moxifloxacin became multinucleated and multiseptated and developed multiple constrictions. These cells stochastically divided multiple times, producing sister-daughter cells phenomenally higher in number than what could be expected from their generation time. This caused an abrupt, unexpectedly high increase in the rifampicin/moxifloxacin resister colonies. This unique cell division behavior was not shown by the rifampicin resisters formed naturally in the actively growing cultures. We could detect such abrupt increases in the antibiotic resisters in others’ and our earlier data on the antibiotic-exposed laboratory/clinical M. tuberculosis strains, M. smegmatis and other bacteria in in vitro cultures, infected macrophages/animals, and tuberculosis patients. However, it went unnoticed/unreported in all those studies. This phenomenon occurring in diverse bacteria surviving against different antibiotics revealed the broad significance of the present study. We speculate that the antibiotic-resistant bacillary clones, which emerge in patients with diverse bacterial infections, might be using the same mechanism to establish an antibiotic resister population quickly in the continued presence of antibiotics. IMPORTANCE The bacterial pathogens that are tolerant to antibiotics and survive in the continued presence of antibiotics have the chance to acquire genetically resistant mutations against the antibiotics and emerge de novo as antibiotic resisters. Once the antibiotic resister clone has emerged, often with compromise on growth characteristics, for the protection of the species, it is important to establish an antibiotic-resistant population quickly in the continued presence of the antibiotic. In this regard, the present study has unraveled multinucleation and multiseptation followed by multiple constrictions as the cellular processes used by the bacteria for quick multiplication to establish antibiotic-resistant populations. The study also points out the same phenomenon occurring in other bacterial systems investigated in our laboratory and others’ laboratories. Identification of these specific cellular events involved in quick multiplication offers additional cellular processes that can be targeted in combination with the existing antibiotics’ targets to preempt the emergence of antibiotic-resistant bacterial strains.
format	article
author	Kishor Jakkala Avraneel Paul Atul Pradhan Rashmi Ravindran Nair Deepti Sharan Sharmada Swaminath Parthasarathi Ajitkumar
author_facet	Kishor Jakkala Avraneel Paul Atul Pradhan Rashmi Ravindran Nair Deepti Sharan Sharmada Swaminath Parthasarathi Ajitkumar
author_sort	Kishor Jakkala
title	Unique Mode of Cell Division by the Mycobacterial Genetic Resister Clones Emerging <italic toggle="yes">De Novo</italic> from the Antibiotic-Surviving Population
title_short	Unique Mode of Cell Division by the Mycobacterial Genetic Resister Clones Emerging <italic toggle="yes">De Novo</italic> from the Antibiotic-Surviving Population
title_full	Unique Mode of Cell Division by the Mycobacterial Genetic Resister Clones Emerging <italic toggle="yes">De Novo</italic> from the Antibiotic-Surviving Population
title_fullStr	Unique Mode of Cell Division by the Mycobacterial Genetic Resister Clones Emerging <italic toggle="yes">De Novo</italic> from the Antibiotic-Surviving Population
title_full_unstemmed	Unique Mode of Cell Division by the Mycobacterial Genetic Resister Clones Emerging <italic toggle="yes">De Novo</italic> from the Antibiotic-Surviving Population
title_sort	unique mode of cell division by the mycobacterial genetic resister clones emerging <italic toggle="yes">de novo</italic> from the antibiotic-surviving population
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/c0074690c9f24c92929f11a46150eaae
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Unique Mode of Cell Division by the Mycobacterial Genetic Resister Clones Emerging <italic toggle="yes">De Novo</italic> from the Antibiotic-Surviving Population

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