Disruption of Mycobactin Biosynthesis Leads to Attenuation of Mycobacterium tuberculosis for Growth and Virulence

Reddy, P. Vineel; Puri, Rupangi Verma; Chauhan, Priyanka; Kar, Ritika; Rohilla, Akshay; Khera, Aparna; Tyagi, Anil K.

doi:10.1093/infdis/jit250

Cited by 127Tuberculosis Research and EpidemiologyMicrobial Natural Products and BiosynthesisMycobacterium research and diagnosis

Disruption of Mycobactin Biosynthesis Leads to Attenuation of Mycobacterium tuberculosis for Growth and Virulence

Reddy, P. Vineel, Puri, Rupangi Verma, Chauhan, Priyanka, Kar, Ritika, Rohilla, Akshay, Khera, Aparna, Tyagi, Anil K.·2013·The Journal of Infectious Diseases

DOI 10.1093/infdis/jit250

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Abstract

BACKGROUND: Low iron availability in the host upregulates the mbt gene cluster of Mycobacterium tuberculosis, which is responsible for mycobactin biosynthesis. However, the biological significance of mycobactins in the growth of this pathogen and in disease progression has not been elucidated. METHODS: We have disrupted the mbtE gene (Rv2380c) in the mbt cluster to evaluate the importance of mycobactin biosynthesis in the growth and virulence of M. tuberculosis. RESULTS: The mbtE mutant (MtbΔmbtE) was unable to synthesize mycobactins, displayed an altered colony morphology, and was attenuated for growth in broth culture and in macrophages. Transmission electron microscopy revealed that MtbΔmbtE displayed an altered cell wall permeability. The growth characteristics and colony morphology of MtbΔmbtE were similar to wild type when the medium was supplemented with mycobactins or when MtbΔmbtE was genetically complemented with the mbtE gene. Moreover, guinea pigs infected with MtbΔmbtE exhibited a significantly reduced bacillary load and histopathological damage in the organs, in comparison to M. tuberculosis-infected animals. CONCLUSIONS: This study highlights the importance of mycobactins in the growth and virulence of M. tuberculosis and establishes the enzymes of mycobactin biosynthesis as novel targets for the development of therapeutic interventions against tuberculosis.

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Authors: Reddy, P. V., Puri, R. V., Chauhan, P., Kar, R., Rohilla, A., Khera, A., & Tyagi, A. K.
Affiliations: University of Delhi (IN)
Corresponding author: Reddy, P. Vineel
ORCID: Chauhan, Priyanka
Rohilla, Akshay
Tyagi, Anil K.
Venue: The Journal of Infectious Diseases
Publisher: Oxford University Press (OUP)
Published: 2013-06-20
Volume: 208
Issue: 8
Pages: 1255-1265
ISSN: 0022-1899 (ISSN-L)
1537-6613
DOI: 10.1093/infdis/jit250
OpenAlex: W2141818070
Cited by: 127
References: 41
Citations by year: 2026: 1 · 2025: 9 · 2024: 5 · 2023: 8 · 2022: 11 · 2021: 10 · 2020: 9 · 2019: 11 · 2018: 12 · 2017: 5 · 2016: 9 · 2015: 16 · 2014: 14 · 2013: 6
FWCI: 11.15
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Infectious Diseases (publishedVersion)
PubMed (publishedVersion)
National University of Singapore (submittedVersion)
Funders: University of Pittsburgh
Council of Scientific and Industrial Research, India
All-India Institute of Medical Sciences
Translational Health Science and Technology Institute
Topics: Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
Keywords: Mycobacterium tuberculosis, bacterial virulence, iron limitation, cell wall permeability, macrophage infection, tuberculosis drug targets
MeSH terms: Animals, Cell Line, Female, Genes, Bacterial, Multigene Family, Guinea Pigs, Histocytochemistry, Humans, Monocytes, Mycobacterium tuberculosis, Oxazoles, Gene Deletion, Statistics, Nonparametric, Bacterial Load

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Disruption of Mycobactin Biosynthesis Leads to Attenuation of Mycobacterium tuberculosis for Growth and Virulence

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