Why are bacteria refractory to antimicrobials?

Hogan, Deborah A.; Kolter, Roberto

doi:10.1016/s1369-5274(02)00357-0

Cited by 142 publications

(90 citation statements)

References 62 publications

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“…Increased selection pressure in the contaminated rhizosphere soil also potentially led to an increased expression of genes related to cooperation and communication (quorum sensing and biofilm formation category). Biofilm formation is an essential feature of rhizosphere colonization (Lugtenberg et al, 2001;Ramey et al, 2004) and bacteria living in biofilms have increased resistance to environmental stresses (Costerton et al, 1999;Hogan and Kolter, 2002). Consequently, genes related to biofilm formation were reported to be over-expressed during rhizosphere colonization, and their inactivation led to reduced fitness (Matilla et al, 2007;Ramachandran et al, 2011;Fan et al, 2012).…”

Section: Metatranscriptomics Of the Rhizospherementioning

confidence: 99%

Microbial expression profiles in the rhizosphere of willows depend on soil contamination

et al. 2013

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The goal of phytoremediation is to use plants to immobilize, extract or degrade organic and inorganic pollutants. In the case of organic contaminants, plants essentially act indirectly through the stimulation of rhizosphere microorganisms. A detailed understanding of the effect plants have on the activities of rhizosphere microorganisms could help optimize phytoremediation systems and enhance their use. In this study, willows were planted in contaminated and non-contaminated soils in a greenhouse, and the active microbial communities and the expression of functional genes in the rhizosphere and bulk soil were compared. Ion Torrent sequencing of 16S rRNA and Illumina sequencing of mRNA were performed. Genes related to carbon and amino-acid uptake and utilization were upregulated in the willow rhizosphere, providing indirect evidence of the compositional content of the root exudates. Related to this increased nutrient input, several microbial taxa showed a significant increase in activity in the rhizosphere. The extent of the rhizosphere stimulation varied markedly with soil contamination levels. The combined selective pressure of contaminants and rhizosphere resulted in higher expression of genes related to competition (antibiotic resistance and biofilm formation) in the contaminated rhizosphere. Genes related to hydrocarbon degradation were generally more expressed in contaminated soils, but the exact complement of genes induced was different for bulk and rhizosphere soils. Together, these results provide an unprecedented view of microbial gene expression in the plant rhizosphere during phytoremediation.

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Section: Metatranscriptomics Of the Rhizospherementioning

confidence: 99%

Microbial expression profiles in the rhizosphere of willows depend on soil contamination

et al. 2013

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“…The mechanisms underlying the non-inherited antibiotic refractoriness of bacteria are diverse, and only partially understood (Hogan and Kolter, 2002;Lewis, 2010;Balaban et al, 2013;Orman and Brynildsen, 2013). Some forms of tolerance to lethal doses of antibiotics, for example, persistence, are associated with a strongly reduced metabolic activity, whereas others rely on active responses that confer (collective) adaptive resistance (Balaban et al, 2004;Butler et al, 2010;Lewis, 2010;Nguyen et al, 2011;Wakamoto et al, 2013;Meredith et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Density-dependent adaptive resistance allows swimming bacteria to colonize an antibiotic gradient

et al. 2015

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During antibiotic treatment, antibiotic concentration gradients develop. Little is know regarding the effects of antibiotic gradients on populations of nonresistant bacteria. Using a microfluidic device, we show that high-density motile Escherichia coli populations composed of nonresistant bacteria can, unexpectedly, colonize environments where a lethal concentration of the antibiotic kanamycin is present. Colonizing bacteria establish an adaptively resistant population, which remains viable for over 24 h while exposed to the antibiotic. Quantitative analysis of multiple colonization events shows that collectively swimming bacteria need to exceed a critical population density in order to successfully colonize the antibiotic landscape. After colonization, bacteria are not dormant but show both growth and swimming motility under antibiotic stress. Our results highlight the importance of motility and population density in facilitating adaptive resistance, and indicate that adaptive resistance may be a first step to the emergence of genetically encoded resistance in landscapes of antibiotic gradients.

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“…P athogens can develop resistance to drugs directed against microbial targets by modifying the drug, by lowering the concentration of drug that reaches the target, or by mutating the target (1,2). There is also an increasing concern that therapeutics developed for bioterrorism agents may be rendered ineffective if the microbial target is altered intentionally.…”

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confidence: 99%

Polyvalent inhibitors of anthrax toxin that target host receptors

Basha

Rai

Poon

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Resistance of pathogens to antimicrobial therapeutics has become a widespread problem. Resistance can emerge naturally, but it can also be engineered intentionally, which is an important consideration in designing therapeutics for bioterrorism agents. Blocking host receptors used by pathogens represents a powerful strategy to overcome this problem, because extensive alterations to the pathogen may be required to enable it to switch to a new receptor that can still support pathogenesis. Here, we demonstrate a facile method for producing potent receptor-directed antitoxins. We used phage display to identify a peptide that binds both anthraxtoxin receptors and attached this peptide to a synthetic scaffold. Polyvalency increased the potency of these peptides by >50,000-fold in vitro and enabled the neutralization of anthrax toxin in vivo. This work demonstrates a receptor-directed anthrax-toxin inhibitor and represents a promising strategy to combat a variety of viral and bacterial diseases.antimicrobial resistance ͉ phage display ͉ therapeutics P athogens can develop resistance to drugs directed against microbial targets by modifying the drug, by lowering the concentration of drug that reaches the target, or by mutating the target (1, 2). There is also an increasing concern that therapeutics developed for bioterrorism agents may be rendered ineffective if the microbial target is altered intentionally. This problem could be overcome, however, by designing inhibitors that block host proteins used by the pathogen or its toxins to cause disease.Microbial pathogens and their products interact with host structures to facilitate colonization or to promote cellular uptake. Many of these interactions are polyvalent, meaning that they involve the simultaneous binding of multiple ligands on one entity to multiple receptors on another (3). The design of synthetic polyvalent (4-8) or oligovalent (9, 10) molecules also represents a promising approach to enhance the potency of inhibitors of microbial pathogens and toxins. Current examples of this approach have involved the design of molecules that bind directly to the pathogen or toxin. Inhibitors that bind host proteins would represent an effective way to attenuate virulence that may be less susceptible to resistance mechanisms, and the use of polyvalency could provide a significant enhancement in the potency of these inhibitors.ANTXR1 and ANTXR2 are host receptors that bind and internalize anthrax toxin (11,12). These proteins are likely important for anthrax pathogenesis because the toxin impairs the immune response and is responsible for the major symptoms and death associated with anthrax. Thus, blocking these receptors could represent a promising approach to anthrax therapy.ANTXR1 and ANTXR2 are widely expressed type I membrane proteins that bind components of the extracellular matrix (13). They both contain an extracellular I domain, which binds the protective antigen (PA) component of anthrax toxin. The two proteins are 40% identical overall and share 60% identity within ...

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Why are bacteria refractory to antimicrobials?

Cited by 142 publications

References 62 publications

Microbial expression profiles in the rhizosphere of willows depend on soil contamination

Microbial expression profiles in the rhizosphere of willows depend on soil contamination

Density-dependent adaptive resistance allows swimming bacteria to colonize an antibiotic gradient

Polyvalent inhibitors of anthrax toxin that target host receptors

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