Evaluating the Effect of Oxygen Concentrations on Antibiotic Sensitivity, Growth, and Biofilm Formation of Human Pathogens

Gupta, Sudeep; Laskar, Nozrin; Kadouri, Daniel E.

doi:10.4137/mbi.s40767

Cited by 40 publications

(39 citation statements)

References 48 publications

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“…While the exact mechanisms underlining the impact of oxygen on chronic wound biofilms remains to be explored, it remains plausible that lowered oxygen tension and redox potential will favor the proliferation of polymicrobial biofilms in the wound bed (Cramer, 2014). In addition, anoxic or hypoxic conditions have been shown to reduce the efficacies of a range of antibiotics, resulting in reduced biofilm susceptibility (Schaible et al, 2012;Antoniazzi et al, 2016;Gupta et al, 2016). Further contributing to this redox state are excess levels of reactive oxygen species (ROS), which are considered to be a major cause of delayed wound healing.…”

Section: Nutrient and Chemical Factorsmentioning

confidence: 99%

Bioengineered Platforms for Chronic Wound Infection Studies: How Can We Make Them More Human-Relevant?

Kadam

Nadkarni

Lele

et al. 2019

Front. Bioeng. Biotechnol.

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Section: Nutrient and Chemical Factorsmentioning

confidence: 99%

Bioengineered Platforms for Chronic Wound Infection Studies: How Can We Make Them More Human-Relevant?

Kadam

Nadkarni

Lele

et al. 2019

Front. Bioeng. Biotechnol.

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“…Oxygenation plays an important role in bacterial growth, response to environmental cues, and antibiotic susceptibility (Gupta et al, 2016 ). Significantly different oxygen levels are experienced in microfluidic systems and plate-based assays.…”

Section: Resultsmentioning

confidence: 99%

“…Contrastingly, plate-based assays incorporate considerably more oxygen when shaking during incubation. The clinical relevance of bioactivity assay formats must be assessed: while assays are typically performed in ambient oxygen levels, decreased oxygen may be more representative of certain clinical environments (e.g., burns, abscesses, oral cavity) (Gupta et al, 2016 ). Although measured activity differences between microfluidic and plate-based assays are striking and could originate in part from the increased oxygenation with 96-well plates, producing the same activity profiles in different bioassay formats may be irrelevant as no assay format imitates true biological conditions.…”

Section: Resultsmentioning

confidence: 99%

Implementation of Microfluidics for Antimicrobial Susceptibility Assays: Issues and Optimization Requirements

Parsley

Smythers

Hicks

2020

Front. Cell. Infect. Microbiol.

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Despite the continuous emergence of multi-drug resistant pathogens, the number of new antimicrobials reaching the market is critically low. Natural product peptides are a rich source of bioactive compounds, and advances in mass spectrometry have achieved unprecedented capabilities for the discovery and characterization of novel molecular species. However, traditional bioactivity assay formats hinder the discovery and biochemical characterization of natural product antimicrobial peptides (AMPs), necessitating large sample quantities and significant optimization of experimental parameters to achieve accurate/consistent activity measurements. Microfluidic devices offer a promising alternative to bulk assay systems. Herein, a microfluidics-based bioassay was compared to the traditional 96-well plate format in respective commercially-available hardware. Bioactivity in each assay type was compared using a Viola inconspicua peptide library screened against E. coli ATCC 25922. Brightfield microcopy was used to determine bioactivity in microfluidic channels while both common optical and fluorescence-based measurements of cell viability were critically assessed in plate-based assays. Exhibiting some variation in optical density and fluorescence-based measurements, all plate-based assays conferred bioactivity in late eluting V. inconspicua library fractions. However, significant differences in the bioactivity profiles of plate-based and microfluidic assays were found, and may be derived from the materials comprising each assay device or the growth/assay conditions utilized in each format. While new technologies are necessary to overcome the limitations of traditional bioactivity assays, we demonstrate that off-the-shelf implementation of microfluidic devices is non-trivial and significant method development/optimization is required before conventional use can be realized for sensitive and rapid detection of AMPs in natural product matrices.

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“…In addition, intrinsic factors related to the bacteria in the biofilm state, such as reduced metabolic activity, slower growth rates and formation of highly-tolerant persister cells and small-colony variants, also contribute to this state of resistance [31]. Further, as discussed previously, microenvironmental factors such as poor oxygenation, pH variation and increased oxidative stress, could decrease the distribution, availability and thereby the efficacy of antibiotics in the chronic wound bed [32,33]. Given this inherent recalcitrance of chronic wound biofilms to antibiotics, expanding the arsenal of antibiotics or developing novel antibiotic regimens, will have limited effect.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Non-Conventional Antimicrobial Approaches for Chronic Wound Biofilms: Have We Found the ‘Chink in the Armor’?

Kadam¹,

Shai

Shahane

et al. 2019

Biomedicines

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Chronic wounds are a major healthcare burden, with huge public health and economic impact. Microbial infections are the single most important cause of chronic, non-healing wounds. Chronic wound infections typically form biofilms, which are notoriously recalcitrant to conventional antibiotics. This prompts the need for alternative or adjunct ‘anti-biofilm’ approaches, notably those that account for the unique chronic wound biofilm microenvironment. In this review, we discuss the recent advances in non-conventional antimicrobial approaches for chronic wound biofilms, looking beyond standard antibiotic therapies. These non-conventional strategies are discussed under three groups. The first group focuses on treatment approaches that directly kill or inhibit microbes in chronic wound biofilms, using mechanisms or delivery strategies distinct from antibiotics. The second group discusses antimicrobial approaches that modify the biological, chemical or biophysical parameters in the chronic wound microenvironment, which in turn enables the disruption and removal of biofilms. Finally, therapeutic approaches that affect both, biofilm bacteria and microenvironment factors, are discussed. Understanding the advantages and limitations of these recent approaches, their stage of development and role in biofilm management, could lead to new treatment paradigms for chronic wound infections. Towards this end, we discuss the possibility that non-conventional antimicrobial therapeutics and targets could expose the ‘chink in the armor’ of chronic wound biofilms, thereby providing much-needed alternative or adjunct strategies for wound infection management.

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Evaluating the Effect of Oxygen Concentrations on Antibiotic Sensitivity, Growth, and Biofilm Formation of Human Pathogens

Cited by 40 publications

References 48 publications

Bioengineered Platforms for Chronic Wound Infection Studies: How Can We Make Them More Human-Relevant?

Bioengineered Platforms for Chronic Wound Infection Studies: How Can We Make Them More Human-Relevant?

Implementation of Microfluidics for Antimicrobial Susceptibility Assays: Issues and Optimization Requirements

Recent Advances in Non-Conventional Antimicrobial Approaches for Chronic Wound Biofilms: Have We Found the ‘Chink in the Armor’?

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