1887

Abstract

Bacteria use population heterogeneity, the presence of more than one phenotypic variant in a clonal population, to endure diverse environmental challenges – a ‘bet-hedging’ strategy. Phenotypic variants have been described in many bacteria, but the phenomenon is not well-understood in mycobacteria, including the environmental factors that influence heterogeneity. Here, we describe three reproducible morphological variants in – smooth, rough, and an intermediate morphotype that predominated under typical laboratory conditions. has two recognized morphotypes, smooth and rough. Interestingly, exists in only a rough form. The shift from smooth to rough in both and was observed over time in extended static culture, however the frequency of the rough morphotype was high in pellicle preparations compared to planktonic culture, suggesting a role for an aggregated microenvironment in the shift to the rough form. Differences in growth rate, biofilm formation, cell wall composition, and drug tolerance were noted among and variants. Deletion of the global regulator shifted the intermediate morphotype to a smooth form but did not fully phenocopy the naturally generated smooth morphotype, indicating Lsr2 is likely downstream of the initiating regulatory cascade that controls these morphotypes. Rough forms typically correlate with higher invasiveness and worse outcomes during infection and our findings indicate the shift to this rough form is promoted by aggregation. Our findings suggest that mycobacterial population heterogeneity, reflected in colony morphotypes, is a reproducible, programmed phenomenon that plays a role in adaptation to unique environments and this heterogeneity may influence infection progression and response to treatment.

Funding
This study was supported by the:
  • National Institute of Allergy and Infectious Diseases (Award R21AI120458)
    • Principle Award Recipient: MartinI. Voskuil
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2023-10-20
2024-07-23
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