Abstract:
:Mycobacterium tuberculosis (Mtb) infection results in a spectrum of clinical and histopathologic manifestations. It has been proposed that the environmental and immune pressures associated with different contexts of infection have different consequences for the associated bacterial populations, affecting drug susceptibility and the emergence of resistance. However, there is little concrete evidence for this model. We prospectively collected sputum samples from 18 newly diagnosed and treatment-naïve patients with tuberculosis and sequenced 795 colony-derived Mtb isolates. Mutant accumulation rates varied considerably between different bacilli isolated from the same individual, and where high rates of mutation were observed, the mutational spectrum was consistent with reactive oxygen species-induced mutagenesis. Elevated bacterial mutation rates were identified in isolates from HIV-negative but not HIV-positive individuals, suggesting that they were immune-driven. These results support the model that mutagenesis of Mtb in vivo is modulated by the host environment, which could drive the emergence of variants associated with drug resistance in a host-dependent manner.
journal_name
Sci Advjournal_title
Science advancesauthors
Liu Q,Wei J,Li Y,Wang M,Su J,Lu Y,López MG,Qian X,Zhu Z,Wang H,Gan M,Jiang Q,Fu YX,Takiff HE,Comas I,Li F,Lu X,Fortune SM,Gao Qdoi
10.1126/sciadv.aba4901subject
Has Abstractpub_date
2020-05-29 00:00:00pages
eaba4901issue
22issn
2375-2548pii
aba4901journal_volume
6pub_type
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