Journal
FUTURE MEDICINAL CHEMISTRY
Volume 8, Issue 10, Pages 1133-1151Publisher
FUTURE SCI LTD
DOI: 10.4155/fmc-2016-0027
Keywords
antibiotic resistance; beta-lactamase; collateral sensitivity; cross-resistance; efflux pump inhibitor; EPI; intrinsic resistome; multidrug efflux pump; persistence; resistome
Categories
Funding
- Spanish Ministry of Economy and Competitivity
- Madrid Autonomous Community [S2010/BMD2414 [PROMPT]]
- Instituto de Salud Carlos III (Spanish Network for Research on Infectious Diseases [REIPI RD12/0015]
- EU [HEALTH-F3-2011-282004 [EVOTAR]]
- European Social Fund
- MINECO
- [BIO2014-54507-R]
- [JPI Water StARE JPIW2013-089-C02-01]
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Most efforts in the development of antimicrobials have focused on the screening of lethal targets. Nevertheless, the constant expansion of antimicrobial resistance makes the antibiotic resistance determinants themselves suitable targets for finding inhibitors to be used in combination with antibiotics. Among them, inhibitors of antibiotic inactivating enzymes and of multidrug efflux pumps are suitable candidates for improving the efficacy of antibiotics. In addition, the application of systems biology tools is helping to understand the changes in bacterial physiology associated to the acquisition of resistance, including the increased susceptibility to other antibiotics displayed by some antibiotic-resistant mutants. This information is useful for implementing novel strategies based in metabolic interventions or combination of antibiotics for improving the efficacy of antibacterial therapy.
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