Antimicrobial interactions: mechanisms and implications for drug discovery and resistance evolution

Bollenbach, Tobias

doi:10.1016/j.mib.2015.05.008

Cited by 225 publications

(164 citation statements)

References 86 publications

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“…Antibiotic treatment outcomes are diverse in multidrug environments, and previous exposure to an antibiotic can alter the efficacy of other antibiotics [104]. Studies on multidrug contexts highlight the roles of cellular respiration [34], ATP synthesis and polysaccharide synthesis [69] in determining treatment efficacy.…”

Section: Environmental Factorsmentioning

confidence: 99%

Antibiotic efficacy — context matters

Yang

Bening

Collins

2017

Current Opinion in Microbiology

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Antibiotic lethality is a complex physiological process, sensitive to external cues. Recent advances using systems approaches have revealed how events downstream of primary target inhibition actively participate in antibiotic death processes. In particular, altered metabolism, translational stress and DNA damage each contribute to antibiotic-induced cell death. Moreover, environmental factors such as oxygen availability, extracellular metabolites, population heterogeneity and multidrug contexts alter antibiotic efficacy by impacting bacterial metabolism and stress responses. Here we review recent studies on antibiotic efficacy and highlight insights gained on the involvement of cellular respiration, redox stress and altered metabolism in antibiotic lethality. We discuss the complexity found in natural environments and highlight knowledge gaps in antibiotic lethality that may be addressed using systems approaches.

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Section: Environmental Factorsmentioning

confidence: 99%

Antibiotic efficacy — context matters

Yang

Bening

Collins

2017

Current Opinion in Microbiology

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“…97,98 The functionalization of NPs using antibiotics (Table 3) is not only a promising nanoplatform to combat bacterial resistance but may also reduce the dose and hence toxicity of the drugs. NPs target or deliver antimicrobial agents to the infected site, thereby overcoming resistance as well as mitigating their hazardous impact on normal cells.…”

mentioning

confidence: 99%

Nanomaterials for alternative antibacterial therapy

Hemeg

2017

IJN

441

262

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Despite an array of cogent antibiotics, bacterial infections, notably those produced by nosocomial pathogens, still remain a leading factor of morbidity and mortality around the globe. They target the severely ill, hospitalized and immunocompromised patients with incapacitated immune system, who are prone to infections. The choice of antimicrobial therapy is largely empirical and not devoid of toxicity, hypersensitivity, teratogenicity and/or mutagenicity. The emergence of multidrug-resistant bacteria further intensifies the clinical predicament as it directly impacts public health due to diminished potency of current antibiotics. In addition, there is an escalating concern with respect to biofilm-associated infections that are refractory to the presently available antimicrobial armory, leaving almost no therapeutic option. Hence, there is a dire need to develop alternate antibacterial agents. The past decade has witnessed a substantial upsurge in the global use of nanomedicines as innovative tools for combating the high rates of antimicrobial resistance. Antibacterial activity of metal and metal oxide nanoparticles (NPs) has been extensively reported. The microbes are eliminated either by microbicidal effects of the NPs, such as release of free metal ions culminating in cell membrane damage, DNA interactions or free radical generation, or by microbiostatic effects coupled with killing potentiated by the host’s immune system. This review encompasses the magnitude of multidrug resistance in nosocomial infections, bacterial evasion of the host immune system, mechanisms used by bacteria to develop drug resistance and the use of nanomaterials based on metals to overcome these challenges. The diverse annihilative effects of conventional and biogenic metal NPs for antibacterial activity are also discussed. The use of polymer-based nanomaterials and nanocomposites, alone or functionalized with ligands, antibodies or antibiotics, as alternative antimicrobial agents for treating severe bacterial infections is also discussed. Combinatorial therapy with metallic NPs, as adjunct to the existing antibiotics, may aid to restrain the mounting menace of bacterial resistance and nosocomial threat.

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“…Combination of antimicrobials offers a potential for increasing antimicrobial treatment efficacy and for reducing resistance evolution [26]. Synergy between colistin and other antibiotics have been reported [27] [28]. We have tested the combinatorial effect of L-thanatin and colistin against colistin-resistant E. coli but only found concentration-dependent additive effect at certain combinations.…”

Section: Discussionmentioning

confidence: 95%

Linear Thanatin Is an Effective Antimicrobial Peptide against Colistin-Resistant <i>Escherichia coli in Vitro</i>

Zhou¹,

Fan²,

Lu³

et al. 2018

AiM

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Colistin has been regarded as the last line antibiotic for treatment of infections caused by multidrug resistant gram-negative bacteria. Therefore, the increasing emergence of colistin resistance among gram-negative bacteria represents a serious problem. The objective of this study was to characterize the effectiveness of the chemically synthesized thanatin in linear form against colistin-resistant E. coli isolated from a pig farm in China. Agar diffusion assay and broth microdilution test were employed to analyze the susceptibility of colistin-sensitive E. coli (ATCC25922) and colistin-resistant E. coli (SHP45) to linear thanatin (L-thanatin). Combinatory effect of linear thanatin and colistin against E. coli was also determined by fractional inhibition concentration index (FICI) analysis. The results showed that L-thanatin at a concentration of 1 mg/ml produced larger inhibition zone on agar against ATCC25922 than SHP45. In the quantitative microdilution test, L-thanatin had the same MIC of 3.2 µg/ml for ATCC25922 and SHP45. Based on the FICI analysis, additive effect was obtained with 1.56 µg/ml of L-thanatin and 0.125 µg/ml of colistin for ATCC25922; but with 1.56 µg/ml of L-thanatin and 0.25 µg/ml of colistin or with 2 µg/ml of colistin and 0.39 µg/ml of L-thanatin for SHP45. These data proved that L-thanatin is an effective antimicrobial peptide against colistin-resistant E. coli.

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Antimicrobial interactions: mechanisms and implications for drug discovery and resistance evolution

Cited by 225 publications

References 86 publications

Antibiotic efficacy — context matters

Antibiotic efficacy — context matters

Nanomaterials for alternative antibacterial therapy

Linear Thanatin Is an Effective Antimicrobial Peptide against Colistin-Resistant <i>Escherichia coli in Vitro</i>

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Antimicrobial interactions: mechanisms and implications for drug discovery and resistance evolution

Cited by 225 publications

References 86 publications

Antibiotic efficacy — context matters

Antibiotic efficacy — context matters

Nanomaterials for alternative antibacterial therapy

Linear Thanatin Is an Effective Antimicrobial Peptide against Colistin-Resistant &lt;i&gt;Escherichia coli in Vitro&lt;/i&gt;

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Linear Thanatin Is an Effective Antimicrobial Peptide against Colistin-Resistant <i>Escherichia coli in Vitro</i>