Abstract
Emergence of antibiotic resistant pathogenic bacteria poses a serious public health challenge worldwide. However, antibiotic resistance genes are not confined to the clinic; instead they are widely prevalent in different bacterial populations in the environment. Therefore, to understand development of antibiotic resistance in pathogens, we need to consider important reservoirs of resistance genes, which may include determinants that confer self-resistance in antibiotic producing soil bacteria and genes encoding intrinsic resistance mechanisms present in all or most non-producer environmental bacteria. While the presence of resistance determinants in soil and environmental bacteria does not pose a threat to human health, their mobilization to new hosts and their expression under different contexts, for example their transfer to plasmids and integrons in pathogenic bacteria, can translate into a problem of huge proportions, as discussed in this review. Selective pressure brought about by human activities further results in enrichment of such determinants in bacterial populations. Thus, there is an urgent need to understand distribution of resistance determinants in bacterial populations, elucidate resistance mechanisms, and determine environmental factors that promote their dissemination. This comprehensive review describes the major known self-resistance mechanisms found in producer soil bacteria of the genus Streptomyces and explores the relationships between resistance determinants found in producer soil bacteria, non-producer environmental bacteria, and clinical isolates. Specific examples highlighting potential pathways by which pathogenic clinical isolates might acquire these resistance determinants from soil and environmental bacteria are also discussed. Overall, this article provides a conceptual framework for understanding the complexity of the problem of emergence of antibiotic resistance in the clinic. Availability of such knowledge will allow researchers to build models for dissemination of resistance genes and for developing interventions to prevent recruitment of additional or novel genes into pathogens.
Highlights
A BRIEF HISTORICAL PERSPECTIVESelman Waksman, a prominent researcher in the field of actinomycetes in the early part of the twentieth century, described the term antibiotic as a chemical compound generated from microorganisms that inhibits or destroys other microbes (Hopwood, 2007; Davies and Davies, 2010)
There is an urgent need to understand distribution of resistance determinants in bacterial populations, elucidate resistance mechanisms, and determine environmental factors that promote their dissemination. This comprehensive review describes the major known self-resistance mechanisms found in producer soil bacteria of the genus Streptomyces and explores the relationships between resistance determinants found in producer soil bacteria, non-producer environmental bacteria, and clinical isolates
The presence of β-lactamases in producers presents an evolutionary conundrum – how can β-lactams and β-lactamases co-exist simultaneously in producer cells? Perhaps these enzymes play alternative cellular functions in Streptomyces, are expressed at low levels, or are expressed in a growth phase different from biosynthesis? Overall, it has been proposed that β-lactamases may not play an important role in resistance in Streptomyces species, which may instead involve the function of low-affinity penicillin binding proteins (PBPs) (Ogawara, 2015) discussed in Section “Target Modification/Bypass/Protection Mechanisms” in this article
Summary
Reviewed by: Maite Muniesa, University of Barcelona, Spain Francisco Dionisio, Universidade de Lisboa, Portugal. There is an urgent need to understand distribution of resistance determinants in bacterial populations, elucidate resistance mechanisms, and determine environmental factors that promote their dissemination. This comprehensive review describes the major known self-resistance mechanisms found in producer soil bacteria of the genus Streptomyces and explores the relationships between resistance determinants found in producer soil bacteria, non-producer environmental bacteria, and clinical isolates. This article provides a conceptual framework for understanding the complexity of the problem of emergence of antibiotic resistance in the clinic Availability of such knowledge will allow researchers to build models for dissemination of resistance genes and for developing interventions to prevent recruitment of additional or novel genes into pathogens
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