Drug Resistant and Persistent Tuberculosis: Mechanisms and Drug Development

Zhang, Ying

doi:10.1007/978-1-4614-1400-1_22

Cited by 5 publications

(3 citation statements)

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This phenotypic drug tolerance is associated with the phenomenon of persisters, a small sub-population of cells with distinct but as-yet-unknown metabolic or physiological states. Persisters are genetically identical with susceptible counterparts and able to convert to susceptible cells upon restoration of normal environments (Lewis 2008; Zhang 2012). …”

Section: Epigenetic Drug Tolerancementioning

confidence: 99%

Molecular Biology of Drug Resistance in Mycobacterium tuberculosis

Smith

Wolff

Nguyen

2012

Current Topics in Microbiology and Immunology

134

170

View full text Add to dashboard Cite

Tuberculosis (TB) has become a curable disease thanks to the discovery of antibiotics. However, it has remained one of the most difficult infections to treat. Most current TB regimens consist of six to nine months of daily doses of four drugs that are highly toxic to patients. The purpose of these lengthy treatments is to completely eradicate Mycobacterium tuberculosis, notorious for its ability to resist most antibacterial agents, thereby preventing the formation of drug resistant mutants. On the contrary, the prolonged therapies have led to poor patient adherence. This, together with a severe limit of drug choices, has resulted in the emergence of strains that are increasingly resistant to the few available antibiotics. Here we review our current understanding of molecular mechanisms underlying the profound drug resistance of M. tuberculosis. This knowledge is essential for the development of more effective antibiotics that not only are potent against drug resistant M. tuberculosis strains but also help shorten the current treatment courses required for drug susceptible TB.

show abstract

Section: Epigenetic Drug Tolerancementioning

confidence: 99%

Molecular Biology of Drug Resistance in Mycobacterium tuberculosis

Smith

Wolff

Nguyen

2012

Current Topics in Microbiology and Immunology

134

170

View full text Add to dashboard Cite

show abstract

“…At the same time, M. tuberculosis must activate sufficient immune effector functions to induce granuloma formation in the lung [22, 39–42]. The mechanisms by which bacilli survive the hostile environment and transition in to dormancy are not well understood.…”

Section: Sulfur and Mycobacterial Survivalmentioning

confidence: 99%

New Targets and Inhibitors of Mycobacterial Sulfur Metabolism

Paritala¹,

Carroll²

2013

IDDT

View full text Add to dashboard Cite

The identification of new antibacterial targets is urgently needed to address multidrug resistant and latent tuberculosis infection. Sulfur metabolic pathways are essential for survival and the expression of virulence in many pathogenic bacteria, including Mycobacterium tuberculosis. In addition, microbial sulfur metabolic pathways are largely absent in humans and therefore, represent unique targets for therapeutic intervention. In this review, we summarize our current understanding of the enzymes associated with the production of sulfated and reduced sulfur-containing metabolites in Mycobacteria. Small molecule inhibitors of these catalysts represent valuable chemical tools that can be used to investigate the role of sulfur metabolism throughout the Mycobacterial lifecycle and may also represent new leads for drug development. In this light, we also summarize recent progress made in the development of inhibitors of sulfur metabolism enzymes.

show abstract

“…In the past decade, with a broadened scope of investigation, both population- and organism-based studies have illustrated that commensal bacteria likely have played a key role in AR ecology ( Andremont, 2003 ; Wang et al, 2006 ; Wang and Schaffner, 2011 ). With the expansion of research territory, AR has been found prevalent across the ecosystem, from clinical samples, animal and human hosts, retail foods, to waste water, soil, and other natural environment ( Zhanel et al, 2000 ; Österblad et al, 2001 ; Aubry-Damon et al, 2004 ; Wang et al, 2006 ; Koike et al, 2007 ; Sommer et al, 2009 ; Li and Wang, 2010 ; D’Costa et al, 2011 ; Zhang, 2011 ; Ye et al, 2013 ). For instance, using non-specific culturing methods and culture-independent real-time PCR, the abundance of AR in the food chain was revealed and a broad-spectrum of non-pathogenic and even beneficial bacteria were found carrying transmissible AR genes ( Duran and Marshall, 2005 ; Wang et al, 2006 ; Manuzon et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Characterization of antibiotic resistance in commensal bacteria from an aquaculture ecosystem

et al. 2015

View full text Add to dashboard Cite

The objective of the study was to improve the understanding of antibiotic resistance (AR) ecology through characterization of antibiotic-resistant commensal isolates associated with an aquaculture production system. A total of 4767 isolates non-susceptible to sulfamethoxazole/trimethoprim (Sul/Tri), tetracycline (Tet), erythromycin (Erm), or cefotaxime (Ctx), originated from fish, feed, and environmental samples of an aquaculture farm with no known history of antibiotic applications were examined. Close to 80% of the isolates exhibited multi-drug resistance in media containing the corresponding antibiotics, and representative AR genes were detected in various isolates by PCR, with feed isolates had the highest positive rate detected. Identified AR gene carriers involved 18 bacterial genera. Selected AR genes led to acquired resistance in other bacteria by transformation. The AR traits in many isolates were stable in the absence of selective pressure. AR-rich feed and possibly environmental factors may contribute to AR in the aquaculture ecosystem. For minimum inhibitory concentration test, brain heart infusion medium was found more suitable for majority of the bacteria examined than cation-adjusted Mueller Hinton broth, with latter being the recommended medium for clinical isolates by standard protocol. The data indicated a need to update the methodology due to genetic diversity of microbiota for better understanding of the AR ecology.

show abstract

Drug Resistant and Persistent Tuberculosis: Mechanisms and Drug Development

Cited by 5 publications

References 128 publications

Molecular Biology of Drug Resistance in Mycobacterium tuberculosis

Molecular Biology of Drug Resistance in Mycobacterium tuberculosis

New Targets and Inhibitors of Mycobacterial Sulfur Metabolism

Characterization of antibiotic resistance in commensal bacteria from an aquaculture ecosystem

Contact Info

Product

Resources

About