Bacteria commonly live in dense and genetically diverse communities associated with surfaces. In these communities, competition for resources and space is intense, and yet we understand little of how this affects the spread of antibiotic-resistant strains. Here, we study interactions between antibiotic-resistant and susceptible strains using in vitro competition experiments in the opportunistic pathogen Pseudomonas aeruginosa and in silico simulations. Selection for intracellular resistance to streptomycin is very strong in colonies, such that resistance is favoured at very low antibiotic doses. In contrast, selection for extracellular resistance to carbenicillin is weak in colonies, and high doses of antibiotic are required to select for resistance. Manipulating the density and spatial structure of colonies reveals that this difference is partly explained by the fact that the local degradation of carbenicillin by β-lactamase-secreting cells protects neighbouring sensitive cells from carbenicillin. In addition, we discover a second unexpected effect: the inducible elongation of cells in response to carbenicillin allows sensitive cells to better compete for the rapidly growing colony edge. These combined effects mean that antibiotic treatment can select against antibiotic-resistant strains, raising the possibility of treatment regimes that suppress sensitive strains while limiting the rise of antibiotic resistance. We argue that the detailed study of bacterial interactions will be fundamental to understanding and overcoming antibiotic resistance.
Background Rising antimicrobial resistance (AMR) is a threat to modern medicine, and increasing international mobility facilitates the spread of AMR. Infections with resistant organisms have higher morbidity and mortality, are costlier to treat, result in longer hospital stays and place a greater burden on health systems than infections caused by susceptible organisms. Here we review the role of travel in the international dissemination of AMR and consider actions at the levels of travelers, travel medicine practitioners and policymakers that would mitigate this threat. Results Resistant pathogens do not recognize international borders; travelers to areas with high AMR prevalence are likely to be exposed to resistant bacteria and return to their home countries colonized. Medical tourists go between health facilities with drastically different rates of AMR, potentially transmitting highly resistant strains. Drug-resistant bacteria have been found in every continent; however, differences between countries in the prevalence of AMR depend on multiple factors. These include levels of antibiotic consumption (including inappropriate use), access to clean water, adequate sanitation, vaccination coverage, the availability of quality healthcare and access to high-quality medical products. Conclusions Travelers to areas with high levels of AMR should have vaccines up to date, be aware of ways of treating and preventing travelers’ diarrhea (other than antibiotic use) and be informed on safe sexual practices. The healthcare systems of low- and middle-income countries require investment to reduce the transmission of resistant strains by improving access to clean water, sanitation facilities and vaccines. Efforts are needed to curb inappropriate antibiotic use worldwide. In addition, more surveillance is needed to understand the role of the movement of humans, livestock and food products in resistance transmission. The travel medicine community has a key role to play in advocating for the recognition of AMR as a priority on the international health agenda. Key policy recommendations AMR is a threat to modern medicine, and international travel plays a key role in the spread of highly resistant strains. It is essential that this is addressed at multiple levels. Individual travelers can reduce antibiotic consumption and the likelihood of infection. Travelers should have up-to-date vaccines and be informed on methods of preventing and treating travelers’ diarrhea, other than use of antibiotics and on safe sexual practices, such as condom use. Healthcare facilities need to be aware of the travel history of patients to provide appropriate treatment to those who are at high risk of exposure and to prevent further spread. Internationally, in countries without reliable and universal access to clean water, sanitation and hygiene, investment is needed to reduce the emergence and spread of resistance and ensure the antimicrobials available are of assured quality. High-income countries must ensure their use of antimicrobials is appropriate to reduce selection for AMR. Surveillance across all countries is needed to monitor and respond to this emerging threat.
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