Meiotic drive does not impede success in sperm competition in the stalk-eyed fly, Teleopsis dalmanni.

Male X-linked meiotic drive systems, which cause the degeneration of Y-bearing sperm, are common in the Diptera. Sperm killing is typically associated with fitness costs that arise from the destruction of wildtype sperm and collateral damage to maturing drive sperm, resulting in poor success under sperm competition. We investigate X-linked meiotic drive fertility in the stalk-eyed fly, Teleopsis dalmanni. Drive male paternity was measured in double mating trials under sperm competition against a wildtype male. Drive males sired the same number of offspring as wildtype males, both when mated first or second. This is the first evidence that drive males can compete equally with non-drive males in double matings, challenging the assumption that drive males inevitably suffer reduced fertility. The finding is in accord with previous work showing that the number of sperm per ejaculate transferred to females during non-competitive single matings does not differ between drive and wildtype males, which is likely due to the adaptive evolution of enlarged testes in drive males. Future experiments will determine whether the competitive ability of drive males is maintained under higher rates of female remating likely to be experienced in nature.

Repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-inflammatory drugs.

INTRODUCTION: The number of cases of drug-resistant Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), has risen rapidly in recent years. This has led to the resurgence in repurposing existing drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs), for anti-TB treatment. SOURCES OF DATA: Evidence from novel drug screening in vitro, in vivo, pharmacokinetic/pharmacodynamics analyses and clinical trials has been used for the preparation of this systematic review of the potential of NSAIDs for use as an adjunct in new TB chemotherapies. AREAS OF AGREEMENT: Certain NSAIDs have demonstrated inhibitory properties towards actively replicating, dormant and drug-resistant clinical isolates of M. tuberculosis cells. AREAS OF CONTROVERSY: NSAIDs are a diverse class of drugs, which have reported off-target activities, and their endogenous antimicrobial mechanism(s) of action is still unclear. GROWING POINTS: It is essential that clinical trials of NSAIDs continue, in order to assess their suitability for addition to the current TB treatment regimen. Repurposing molecules such as NSAIDs is a vital, low-risk strategy to combat the trend of rapidly increasing antibiotic resistance.

Repurposing-a ray of hope in tackling extensively drug resistance in tuberculosis.

Tuberculosis (TB) remains a serious concern more than two decades on from when the World Health Organization declared it a global health emergency. The alarming rise of antibiotic resistance in Mycobacterium tuberculosis, the etiological agent of TB, has made it exceedingly difficult to control the disease with the existing portfolio of anti-TB chemotherapy. The development of effective drugs with novel mechanism(s) of action is thus of paramount importance to tackle drug resistance. The development of novel chemical entities requires more than 10 years of research, requiring high-risk investment to become commercially available. Repurposing pre-existing drugs offers a solution to circumvent this mammoth investment in time and funds. In this context, several drugs with known safety and toxicity profiles have been evaluated against the TB pathogen and found to be efficacious against its different physiological states. As the endogenous targets of these drugs in the TB bacillus are most likely to be novel, there is minimal chance of cross-resistance with front-line anti-TB drugs. Also, reports that some of these drugs may potentially have multiple targets means that the possibility of the development of resistance against them is minimal. Thus repurposing existing molecules offers immense promise to tackle extensively drug-resistant TB infections.