Non-canonical mechanisms of antibiotic resistance

Martínez, José Luis; Blázquez, Jesús; Baquero, Fernando

doi:10.1007/bf02111820

Cited by 17 publications

(11 citation statements)

References 54 publications

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“…Thus, knowledge on the changes that occur in bacterial metabolic networks during infection may help us to improve treatments, mainly at locations in the human-body where the amount of free antibiotic is not very high. The fact that mutations both in intergenic regions and mutations in regulatory proteins and sensor systems affected bacterial susceptibility to antibiotics (see Table 1) also supports the concept that in vivo susceptibility [39] might be dependent on the tuning of physiological circuits in response to the inputs received during infection.…”

Section: Resultsmentioning

confidence: 59%

The Neglected Intrinsic Resistome of Bacterial Pathogens

et al. 2008

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Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature.

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Section: Resultsmentioning

confidence: 59%

The Neglected Intrinsic Resistome of Bacterial Pathogens

et al. 2008

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“…Phenotypic resistance is thus defined as a transient situation in which a bacterial population, usually susceptible to antibiotics, is transiently resistant ( Figure 1 ). The elements contributing to this phenotype are a part of the intrinsic resistome that are only unveiled under specific growing conditions (Martinez et al, 1994). Below, some examples of phenotypic resistance are described.…”

Section: Phenotypic Resistancementioning

confidence: 99%

The intrinsic resistome of bacterial pathogens

Olivares¹,

Bernardini²,

et al. 2013

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Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyze recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice.

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“…The location of microorganisms in tissues during infection is an important factor in their exposure to antibiotics. In some cases, organisms are refractory to treatment even if they are classified as susceptible by standard in vitro tests (242). Virulent organisms may invade spaces in which the achievable concentration of antibiotic is low, such as in otitis, sinusitis, and meningitis (186).…”

Section: Vol 15 2002 Strategies In Bacterial Infection 661mentioning

confidence: 99%

Interactions among Strategies Associated with Bacterial Infection: Pathogenicity, Epidemicity, and Antibiotic Resistance

2002

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SUMMARY Infections have been the major cause of disease throughout the history of human populations. With the introduction of antibiotics, it was thought that this problem should disappear. However, bacteria have been able to evolve to become antibiotic resistant. Nowadays, a proficient pathogen must be virulent, epidemic, and resistant to antibiotics. Analysis of the interplay among these features of bacterial populations is needed to predict the future of infectious diseases. In this regard, we have reviewed the genetic linkage of antibiotic resistance and bacterial virulence in the same genetic determinants as well as the cross talk between antibiotic resistance and virulence regulatory circuits with the aim of understanding the effect of acquisition of resistance on bacterial virulence. We also discuss the possibility that antibiotic resistance and bacterial virulence might prevail as linked phenotypes in the future. The novel situation brought about by the worldwide use of antibiotics is undoubtedly changing bacterial populations. These changes might alter the properties of not only bacterial pathogens, but also the normal host microbiota. The evolutionary consequences of the release of antibiotics into the environment are largely unknown, but most probably restoration of the microbiota from the preantibiotic era is beyond our current abilities.

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Non-canonical mechanisms of antibiotic resistance

Cited by 17 publications

References 54 publications

The Neglected Intrinsic Resistome of Bacterial Pathogens

The Neglected Intrinsic Resistome of Bacterial Pathogens

The intrinsic resistome of bacterial pathogens

Interactions among Strategies Associated with Bacterial Infection: Pathogenicity, Epidemicity, and Antibiotic Resistance

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