Explore. Learn. Join the conversation.

Working Group on New TB Drugs

Stop TB Partnership

TB R&D Weekly Update: Some Multidrug-resistant Bacteria More Fit

Silva RF, Mendonc SCM, Carvalho LM, Reis AM, Gordo I, Trindade S, Dionisio F.  Pervasive Sign Epistasis between Conjugative Plasmids and Drug-Resistance Chromosomal Mutations. PLoS Genetics.  2011 July;7(7):1-10.

This week we have an article by researchers from Portugal that suggests that in the case of resistance conferred by plasmids that in some cases resistant bacteria increases its ability to replicate and overall fitness compared to susceptible bacteria.  This may complicate research and control efforts to address the rising problem of multidrug resistance.

Author Summary:

Bacteria can become resistant to antibiotics by spontaneous mutation of chromosomal genes or through the acquisition of horizontally mobile genetic elements, mainly conjugative plasmids. Plasmid-borne resistance is widespread among bacterial pathogens.

Plasmids generally entail a cost to the host, associated with the replication and maintenance of the genetic element and with the expression of its genes. Therefore, in the absence of antibiotic, both plasmids and resistance mutations are often deleterious and confer a fitness cost to the cell. Here we studied epistatic interactions between five natural conjugative plasmids and ten chromosomal mutations conferring resistance to three types of antibiotics, making a total of 50 different combinations of chromosomal mutations and conjugative plasmids. We show that sometimes plasmids confer an advantage to bacterial strains carrying resistance mutations in their chromosome.

This occurs in 32% (16 out of 50) of tested combinations.  Furthermore, in 5 out of 50 plasmid-mutations combinations studied (10%), we observed an increased fitness when a plasmid-bearing bacterial cell acquires a drug-resistant mutation. These examples of sign epistasis are highly unexpected. This work explains, at least in part, how multidrug resistance evolved so rapidly.

Coverage of the study in the news“Super Bacteria? Fighting Resistance Could Be Trickier Than Thought” by Catherine Pearson

 

Additional TB R&D News:

UH Case Medical Center to commence Phase 1 clinical trial on TMC207

Open source drug discovery- A new paradigm of collaborative research in tuberculosis drug development

Seegene Introduces AnyplexTMplus MTB/NTM/DR-TB Real-time Test, a One-Stop Solution for Diagnosing Tuberculosis

Comparison of Xpert MTB/RIF with Other Nucleic Acid Technologies for Diagnosing Pulmonary Tuberculosis in a High HIV Prevalence Setting: A Prospective Study



Leave a Comment