Lung microenvironments harbor phenotypes with distinct treatment responses.

Antimicrobial agents and chemotherapy, Volume: 67, Issue: 9
September 19, 2023
Nicholas D Walter ND, Jackie P Ernest JP, Christian Dide-Agossou C, Allison A Bauman AA, Michelle E Ramey ME, Karen Rossmassler K, Lisa M Massoudi LM, Samantha Pauly S, Reem Al Mubarak R, Martin I Voskuil MI, Firat Kaya F, Jansy P Sarathy JP, Matthew D Zimmerman MD, VĂ©ronique Dartois V, Brendan K Podell BK, Radojka M Savic RM, Gregory T Robertson GT

Tuberculosis lung lesions are complex and harbor heterogeneous microenvironments that influence antibiotic effectiveness. Major strides have been made recently in understanding drug pharmacokinetics in pulmonary lesions, but the bacterial phenotypes that arise under these conditions and their contribution to drug tolerance are poorly understood. A pharmacodynamic marker called the RS ratio quantifies ongoing rRNA synthesis based on the abundance of newly synthesized precursor rRNA relative to mature structural rRNA. Application of the RS ratio in the C3HeB/FeJ mouse model demonstrated that populations residing in different tissue microenvironments are phenotypically distinct and respond differently to drug treatment with rifampin, isoniazid, or bedaquiline. This work provides a foundational basis required to address how anatomic and pathologic microenvironmental niches may contribute to long treatment duration and drug tolerance during the treatment of human tuberculosis.

Courtesy of the U.S. National Library of Medicine