Strategies for combating persister cell and biofilm infections

Wood, Thomas K.

doi:10.1111/1751-7915.12774

Cited by 67 publications

(54 citation statements)

References 33 publications

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“…Biofilms are well-documented to provide bacterial cells protection from a variety of stresses, such as heavy metals, organic solvents, and antimicrobials (2)(3)(4). Biofilms of pathogenic bacteria allow these cells to tolerate higher concentrations of antibiotics (up to 1,000 times) than planktonic cells of the same species, leading to chronic infections and facilitating the development of multidrug-resistant strains, such as "superbugs" (2,5). High-level antibiotic tolerance has been a major focus of previous biofilm research and is viewed as a hallmark characteristic of biofilms (2,5).…”

mentioning

confidence: 99%

Antibiotic Susceptibility of Escherichia coli Cells during Early-Stage Biofilm Formation

Lee

Carnicelli

et al. 2019

J Bacteriol

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Bacteria form complex multicellular structures on solid surfaces known as biofilms, which allow them to survive in harsh environments. A hallmark characteristic of mature biofilms is the high-level antibiotic tolerance (up to 1,000 times) compared with that of planktonic cells. Here, we report our new findings that biofilm cells are not always more tolerant to antibiotics than planktonic cells in the same culture. Specifically, Escherichia coli RP437 exhibited a dynamic change in antibiotic susceptibility during its early-stage biofilm formation. This phenomenon was not strain specific. Upon initial attachment, surface-associated cells became more sensitive to antibiotics than planktonic cells. By controlling the cell adhesion and cluster size using patterned E. coli biofilms, cells involved in the interaction between cell clusters during microcolony formation were found to be more susceptible to ampicillin than cells within clusters, suggesting a role of cell-cell interactions in biofilm-associated antibiotic tolerance. After this stage, biofilm cells became less susceptible to ampicillin and ofloxacin than planktonic cells. However, when the cells were detached by sonication, both antibiotics were more effective in killing the detached biofilm cells than the planktonic cells. Collectively, these results indicate that biofilm formation involves active cellular activities in adaption to the attached life form and interactions between cell clusters to build the complex structure of a biofilm, which can render these cells more susceptible to antibiotics. These findings shed new light on bacterial antibiotic susceptibility during biofilm formation and can guide the design of better antifouling surfaces, e.g., those with micron-scale topographic structures to interrupt cell-cell interactions. IMPORTANCE Mature biofilms are known for their high-level tolerance to antibiotics; however, antibiotic susceptibility of sessile cells during early-stage biofilm formation is not well understood. In this study, we aim to fill this knowledge gap by following bacterial antibiotic susceptibility during early-stage biofilm formation. We found that the attached cells have a dynamic change in antibiotic susceptibility, and during certain phases, they can be more sensitive to antibiotics than planktonic counterparts in the same culture. Using surface chemistry-controlled patterned biofilm formation, cell-surface and cell-cell interactions were found to affect the antibiotic susceptibility of attached cells. Collectively, these findings provide new insights into biofilm physiology and reveal how adaptation to the attached life form may influence antibiotic susceptibility of bacterial cells.

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confidence: 99%

Antibiotic Susceptibility of Escherichia coli Cells during Early-Stage Biofilm Formation

Lee

Carnicelli

et al. 2019

J Bacteriol

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“…The combination of a protective matrix and antibiotic tolerance allows microbes within the biofilm to limit the access of host immune factors and thwart an antimicrobial attack. These properties lead to chronic, recurrent infection and persistent local inflammation . This has led the National Institutes of Health (NIH) to announce biofilms as medically important, attributing over 80% of human infections to biofilms.…”

Section: Biofilms and Chronic Woundsmentioning

confidence: 99%

“…These properties lead to chronic, recurrent infection and persistent local inflammation. [38][39][40] This has led the National Institutes of Health (NIH) to announce biofilms as medically important, attributing over 80% of human infections to biofilms. DFU beds are also often colonized by complex communities of microbes (microbiomes) that can form biofilms, interact with the host immune system, and blunt healing responses.…”

Section: Biofilms and Chronic Woundsmentioning

confidence: 99%

The role of the microbiome in nonhealing diabetic wounds

Kalan

Brennan

2018

Annals of the New York Academy of Sciences

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Wound healing is a highly coordinated and complex process, and there can be devastating consequences if it is interrupted. It is believed that, in combination with host factors, microorganisms in a wound bed can not only impair wound healing but can lead to stalled, chronic wounds. It is hypothesized that the wound microbiota persists in chronic wounds as a biofilm, recalcitrant to antibiotic and mechanical intervention. Cultivation-based methods are the gold standard for identification of pathogens residing in wounds. However, these methods are biased against fastidious organisms, and do not capture the full extent of microbial diversity in chronic wounds. Thus, the link between specific microbes and impaired healing remains tenuous. This is partially because local infection and, more specifically, the formation of a biofilm, is difficult to diagnose. This has led to research efforts aimed at understanding if biofilm formation delays healing and leads to persistent and chronic infection. Circumventing challenges associated with culture-based estimations, advances in high-throughput sequencing analysis has revealed that chronic wounds are host to complex, diverse microbiomes comprising multiple species of bacteria and fungi. Here, we discuss how the use of genomic methodologies to study wound microbiomes has advanced the current understanding of infection and biofilm formation in chronic wounds.

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“…(i) microbial biosensors for diagnosis, monitoring and epidemiology (Chang et al, 2017), (ii) nutritional therapy for persistent diarrhoea (Sarker et al, 2017), (iii) new therapeutic strategies for treatment of infections caused by drug-resistant microbes (Br€ ussow, 2017;Wong and Santiago, 2017) and recurrent infections by persister cells and biofilms (Wood, 2017), (iv) the use of designed bacteria to deliver therapeutics (Alvarez and Fernandez, 2017), (v) use of metal-based antimicrobials (Turner, 2017), (vi) microbiome therapies (Cryan, 2017;O'Toole and Paoli, 2017;Osman, 2017), (vii) use of synbiotics (synergistic combinations of prebiotics and probiotics) in prevention and therapy (Gurry, 2017), (viii) tumour-targeting bacteria-based cancer therapies (Felgner et al, 2017), and (ix) the use of microbial treatment of clinical environment surfaces to reduce drug-resistant pathogen burdens (Caselli, 2017) The BKH is thus a crucial motor of medical advancement and its translation into clinical practice. It will also counteract the current trend in expertise fragmentation and lead to more holistic assessments of patient symptoms, and result in the replacement of linear sequential trial-and-error decision tree treatment schedules, based on patient responses to conventional practice drugs, by treatment schedules based on comprehensive exploration of the multidimensional space of personalized medicine that considers patient genomics/microbiome/ physiology/health status/lifestyle, and all available intervention options and their predicted consequences for different individuals.…”

Section: National Clinical Informatics Centre (Ncic)mentioning

confidence: 99%

The DIY Digital Medical Centre

Timmis

2017

Microbial Biotechnology

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SummaryHealthcare systems worldwide are confronted with major economic, organizational and logistical challenges. Historic evolution of health care has led to significant healthcare sector fragmentation, resulting in systemic inefficiencies and suboptimal resource exploitation. To attain a sustainable healthcare model, fundamental, system‐wide improvements that effectively network, and ensure fulfilment of potential synergies between sectors, and include and facilitate coherent strategic planning and organisation of healthcare infrastructure are needed. Critically, they must be specifically designed to sustainably achieve peak performance within the current policy environment for cost‐control, and efficiency and quality improvement for service delivery. We propose creation of a new healthcare cluster, to be embedded in existing healthcare systems. It consists of (i) local 24/7 walk‐in virtually autonomous do‐it‐yourself Digital Medical Centres performing routine diagnosis, monitoring, prevention, treatment and standardized documentation and health outcome assessment/reporting, which are online interfaced with (ii) regional 24/7 eClinician Centres providing on‐demand clinical supervision/assistance to Digital Medical Centre patients. Both of these are, in turn, online interfaced with (iii) the National Clinical Informatics Centre, which houses the national patient data centre (cloud) and data analysis units that conduct patient‐ and population‐level, personalized and predictive(‐medicine) intervention optimization analyses. The National Clinical Informatics Centre also interfaces with biomedical research and prioritizes and accelerates the translation of new discoveries into clinical practice. The associated Health Policy Innovation and Evaluation Centre rapidly integrates new findings with health policy/regulatory discussions. This new cluster would synergistically link all health system components in a circular format, enable not only access by all arms of the health service to latest patient data, but also automatic algorithm analysis and prediction of clinical development of individual patients, reduce bureaucratic burden on medical professionals by enabling a greater level of focus of their expertise on non‐routine medical tasks, lead to automatic translation of aggregate patient data/new knowledge into medical practice, and orient future evolution of health systems towards greater cohesion/integration and hence efficiency. A central plank of the proposed concept is increased emphasis on reduction of disease incidence and severity, to diminish both patient suffering and treatment costs. This will be achieved at the individual and population levels, through (i) significantly improved access to medical services, (ii) stronger focus on primary and secondary prevention and early treatment measures, and disease susceptibility prediction via personalized medicine, involving inter alia genome analysis at birth and periodic analysis of microbiomes and biomarkers, and integration with other patient health and epidemio...

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Strategies for combating persister cell and biofilm infections

Cited by 67 publications

References 33 publications

Antibiotic Susceptibility of Escherichia coli Cells during Early-Stage Biofilm Formation

Antibiotic Susceptibility of Escherichia coli Cells during Early-Stage Biofilm Formation

The role of the microbiome in nonhealing diabetic wounds

The DIY Digital Medical Centre

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