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These bacteria are unable to grow on solid media but can resuscitate in liquid media. Given the epidemiological success of certain clinical genotype families of Mycobacterium tuberculosis, we hypothesize that different strains may have distinct mechanisms of adaptation and tolerance. We used an in vitro carbon starvation model to determine the propensity of strains from lineages 2 and 4 that included the Beijing and LAM families respectively, to generate DCTB. Beijing strains were associated with a greater propensity to produce DCTB compared to LAM strains. Furthermore, LAM strains required culture filtrate (CF) for resuscitation whilst starved Beijing strains were not dependent on CF. Moreover, Beijing strains showed improved resuscitation with cognate CF, suggesting the presence of unique growth stimulatory molecules in this family. Analysis of starved Beijing and LAM strains showed longer cells, which with resuscitation were restored to a shorter length. Cell wall staining with fluorescent D-amino acids identified strain-specific incorporation patterns, indicating that cell surface remodeling during resuscitation was distinct between clinical strains. Collectively, our data demonstrate that M. tuberculosis clinical strains from different genotype lineages have differential propensities to generate DCTB, which may have implications for TB treatment success.<\/jats:p>","DOI":"10.3390\/pathogens13040318","type":"journal-article","created":{"date-parts":[[2024,4,12]],"date-time":"2024-04-12T09:28:06Z","timestamp":1712914086000},"page":"318","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical Strains of Mycobacterium tuberculosis Representing Different Genotype Families Exhibit Distinct Propensities to Adopt the Differentially Culturable State"],"prefix":"10.3390","volume":"13","author":[{"given":"Bhavna Gowan","family":"Gordhan","sequence":"first","affiliation":[{"name":"Department of Science and Innovation and the National Research Foundation Centre of Excellence for Biomedical TB Research, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2017, South Africa"},{"name":"National Health Laboratory Service, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5969-9392","authenticated-orcid":false,"given":"Kiyasha","family":"Padarath","sequence":"additional","affiliation":[{"name":"Department of Science and Innovation and the National Research Foundation Centre of Excellence for Biomedical TB Research, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2017, South Africa"},{"name":"National Health Laboratory Service, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astika","family":"Sewcharran","sequence":"additional","affiliation":[{"name":"Department of Science and Innovation and the National Research Foundation Centre of Excellence for Biomedical TB Research, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2017, South Africa"},{"name":"National Health Laboratory Service, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"McIvor","sequence":"additional","affiliation":[{"name":"Department of Science and Innovation and the National Research Foundation Centre of Excellence for Biomedical TB Research, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2017, South Africa"},{"name":"National Health Laboratory Service, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"VanNieuwenhze","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Indiana University Bloomington, Bloomington, IN 47405-7000, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyaad","family":"Waja","sequence":"additional","affiliation":[{"name":"Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg 2017, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Martinson","sequence":"additional","affiliation":[{"name":"Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg 2017, South Africa"},{"name":"Center for TB Research, Johns Hopkins University, Baltimore, MD 21218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bavesh Davandra","family":"Kana","sequence":"additional","affiliation":[{"name":"Department of Science and Innovation and the National Research Foundation Centre of Excellence for Biomedical TB Research, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2017, South Africa"},{"name":"National Health Laboratory Service, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1164\/rccm.201604-0769OC","article-title":"Detection and quantification of differentially culturable tubercle bacteria in sputum from patients with tuberculosis","volume":"194","author":"Chengalroyen","year":"2016","journal-title":"Am. 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