A microfluidic approach to study the effect of bacterial interactions on antimicrobial susceptibility in polymicrobial cultures

Mohan, Raju; Sanpitakseree, Chotitath; Desai, Amit; Sevgen, Selami E.; Schroeder, Charles M.; Kenis, Paul J. A.

doi:10.1039/c5ra04092b

Cited by 42 publications

(37 citation statements)

References 71 publications

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“…Microfluidic devices provide the means to study microbial ecology and fabricate micron-scale environments with precisely tuned conditions (Figure 2a). Cocultures have been studied using microfluidics in several ways: generating gradients (Figure 2ai), [26][27][28][29] trapping cells to study interactions ( Figure 2aii), [26,29]creating microhabitats to observe dynamics in particular relationships (e.g. predator-prey, resource-competition), constructing and dispersing biofilms, [30] and high-throughput, droplet-based experiments (Figure 2aiii).…”

Section: A Microfluidicsmentioning

confidence: 99%

“…predator-prey, resource-competition), constructing and dispersing biofilms, [30] and high-throughput, droplet-based experiments (Figure 2aiii). [31] While these devices have the advantage of being parallelizable, [28,32] analysis is typically limited to optical measures of growth. Adapting microfluidic systems to other analytical techniques (e.g.…”

Section: A Microfluidicsmentioning

confidence: 99%

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Better together: engineering and application of microbial symbioses

Hays

Patrick

Ziesack

et al. 2015

Current Opinion in Biotechnology

244

151

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Symbioses provide a way to surpass the limitations of individual microbes. Natural communities exemplify this in symbioses like lichens and biofilms that are robust to perturbations, an essential feature in fluctuating environments. Metabolic capabilities also expand in consortia enabling the division of labor across organisms as seen in photosynthetic and methanogenic communities. In engineered consortia, the external environment provides levers of control for microbes repurposed from nature or engineered to interact through synthetic biology. Consortia have successfully been applied to real-world problems including remediation and energy, however there are still fundamental questions to be answered. It is clear that continued study is necessary for the understanding and engineering of microbial systems that are more than the sum of their parts.

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Section: A Microfluidicsmentioning

confidence: 99%

Section: A Microfluidicsmentioning

confidence: 99%

Better together: engineering and application of microbial symbioses

Hays

Patrick

Ziesack

et al. 2015

Current Opinion in Biotechnology

244

151

View full text Add to dashboard Cite

show abstract

“…These techniques use direct quantification factors (including counting by image analysis13, fluorescence intensity1415 and bacterial proliferation volume16) and indirect factors (including morphology1318 medium viscosity16, bacteria-disrupted secretion1920 and bacterial fluctuations originating from metabolism2122) to efficiently determine the antibiotic susceptibility profiles of bacteria. These techniques require a timeframe of 0.5–4 h to a complete an AST.…”

mentioning

confidence: 99%

Simultaneous and quantitative monitoring of co-cultured Pseudomonas aeruginosa and Staphylococcus aureus with antibiotics on a diffusometric platform

Chung

Wang

Chuang

2017

Sci Rep

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Successful treatments against bacterial infections depend on antimicrobial susceptibility testing (AST). However, conventional AST requires more than 24 h to obtain an outcome, thereby contributing to high patient mortality. An antibiotic therapy based on experiences is therefore necessary for saving lives and escalating the emergence of multidrug-resistant pathogens. Accordingly, a fast and effective drug screen is necessary for the appropriate administration of antibiotics. The mixed pathogenic nature of infectious diseases emphasizes the need to develop an assay system for polymicrobial infections. On this basis, we present a novel technique for simultaneous and quantitative monitoring of co-cultured microorganisms by coupling optical diffusometry with bead-based immunoassays. This simple integration simultaneously achieves a rapid AST analysis for two pathogens. Triple color particles were simultaneously recorded and subsequently analyzed by functionalizing different fluorescent color particles with dissimilar pathogen-specific antibodies. Results suggested that the effect of the antibiotic, gentamicin, on co-cultured Pseudomonas aeruginosa and Staphylococcus aureus was effectively distinguished by the proposed technique. This study revealed a multiplexed and time-saving (within 2 h) platform with a small sample volume (~0.5 μL) and a low initial bacterial count (50 CFU per droplet, ~105 CFU/mL) for continuously monitoring the growth of co-cultured microorganisms. This technique provides insights into timely therapies against polymicrobial diseases in the near future.

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“…A recent study has already shown a similar increase in the AmB MMC against C . albicans mixed planktonic populations [80]. This increase on antimicrobial tolerance observed in mixed cultures can be related to species-related resistance mechanisms (e.g.…”

Section: Discussionmentioning

confidence: 99%

Polymicrobial Ventilator-Associated Pneumonia: Fighting In Vitro Candida albicans-Pseudomonas aeruginosa Biofilms with Antifungal-Antibacterial Combination Therapy

et al. 2017

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The polymicrobial nature of ventilator-associated pneumonia (VAP) is now evident, with mixed bacterial-fungal biofilms colonizing the VAP endotracheal tube (ETT) surface. The microbial interplay within this infection may contribute for enhanced pathogenesis and exert impact towards antimicrobial therapy. Consequently, the high mortality/morbidity rates associated to VAP and the worldwide increase in antibiotic resistance has promoted the search for novel therapeutic strategies to fight VAP polymicrobial infections. Under this scope, this work aimed to assess the activity of mono- vs combinational antimicrobial therapy using one antibiotic (Polymyxin B; PolyB) and one antifungal (Amphotericin B; AmB) agent against polymicrobial biofilms of Pseudomonas aeruginosa and Candida albicans. The action of isolated antimicrobials was firstly evaluated in single- and polymicrobial cultures, with AmB being more effective against C. albicans and PolyB against P. aeruginosa. Mixed planktonic cultures required equal or higher antimicrobial concentrations. In biofilms, only PolyB at relatively high concentrations could reduce P. aeruginosa in both monospecies and polymicrobial populations, with C. albicans displaying only punctual disturbances. PolyB and AmB exhibited a synergistic effect against P. aeruginosa and C. albicans mixed planktonic cultures, but only high doses (256 mg L-1) of PolyB were able to eradicate polymicrobial biofilms, with P. aeruginosa showing loss of cultivability (but not viability) at 2 h post-treatment, whilst C. albicans only started to be inhibited after 14 h. In conclusion, combination therapy involving an antibiotic and an antifungal agent holds an attractive therapeutic option to treat severe bacterial-fungal polymicrobial infections. Nevertheless, optimization of antimicrobial doses and further clinical pharmacokinetics/pharmacodynamics and toxicodynamics studies underpinning the optimal use of these drugs are urgently required to improve therapy effectiveness and avoid reinfection.

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A microfluidic approach to study the effect of bacterial interactions on antimicrobial susceptibility in polymicrobial cultures

Abstract: An easy-to-use, lab-on-a-chip platform to rapidly quantify the efficacy of antibiotics to treat polymicrobial infections.

Cited by 42 publications

References 71 publications

Better together: engineering and application of microbial symbioses

Better together: engineering and application of microbial symbioses

Simultaneous and quantitative monitoring of co-cultured Pseudomonas aeruginosa and Staphylococcus aureus with antibiotics on a diffusometric platform

Polymicrobial Ventilator-Associated Pneumonia: Fighting In Vitro Candida albicans-Pseudomonas aeruginosa Biofilms with Antifungal-Antibacterial Combination Therapy

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