Antibiotic resistance of bacteria in biofilms

Stewart, Philip S.; Costerton, J. W.

doi:10.1016/s0140-6736(01)05321-1

Cited by 3,937 publications

(3,103 citation statements)

References 36 publications

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“…2000; Gruntar et al . 2001; Stewart and Costerton 2001; Jefferson 2004; Murgia and Cinco 2004), although further studies are warranted. The detection of only rounded forms of B. burgdorferi in human specimens indicates the need for further studies assessing a relationship between the presence of atypical forms of Borrelia sp.…”

Section: Discussionmentioning

confidence: 99%

In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia burgdorferi and Borrelia garinii

2015

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AimsLittle is known about the effects of phytochemicals against Borrelia sp. causing Lyme disease. Current therapeutic approach to this disease is limited to antibiotics. This study examined the anti‐borreliae efficacy of several plant‐derived compounds and micronutrients.Methods and ResultsWe tested the efficacy of 15 phytochemicals and micronutrients against three morphological forms of Borrelia burgdoferi and Borrelia garinii: spirochetes, latent rounded forms and biofilm. The results showed that the most potent substances against the spirochete and rounded forms of B. burgdorferi and B. garinii were cis‐2‐decenoic acid, baicalein, monolaurin and kelp (iodine); whereas, only baicalein and monolaurin revealed significant activity against the biofilm. Moreover, cis‐2‐decenoic acid, baicalein and monolaurin did not cause statistically significant cytotoxicity to human HepG2 cells up to 125 μg ml−1 and kelp up to 20 μg ml−1.ConclusionsThe most effective antimicrobial compounds against all morphological forms of the two tested Borrelia sp. were baicalein and monolaurin. This might indicate that the presence of fatty acid and phenyl groups is important for comprehensive antibacterial activity.Significance and Impact of the StudyThis study reveals the potential of phytochemicals as an important tool in the fight against the species of Borrelia causing Lyme disease.

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Section: Discussionmentioning

confidence: 99%

In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia burgdorferi and Borrelia garinii

2015

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“…Second, biofilms could have provided effective resistance mechanism against both phage and antibiotics (Abedon, 2017; Cochran et al., 2000; de Beer, 1997; de Beer et al., 1994; Labrie et al., 2010; Stewart & Costerton, 2001), and hence, selection for this trait could have been especially strong in the combination treatment. To explore the defensive function of biofilms in detail, we found that biofilm populations had higher levels of resistance compared to planktonic populations when exposed top selection by phage or antibiotic independently.…”

Section: Discussionmentioning

confidence: 99%

“…Biofilm formation has also been shown to be an effective general resistance mechanism against phages (Stewart & Costerton, 2001; Vidakovic, Singh, Hartmann, Nadell, & Drescher, 2018). Similar to antibiotics, extracellular polysaccharides and proteins could prevent phage adsorption to its receptors while metabolically less active cells are less likely to get infected (Abedon, 2017; Labrie, Samson, & Moineau, 2010).…”

Section: Introductionmentioning

confidence: 99%

Rapid evolution of generalized resistance mechanisms can constrain the efficacy of phage–antibiotic treatments

Moulton‐Brown

Friman

2018

Evolutionary Applications

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Antimicrobial resistance has been estimated to be responsible for over 700,000 deaths per year; therefore, new antimicrobial therapies are urgently needed. One way to increase the efficiency of antibiotics is to use them in combination with bacteria‐specific parasitic viruses, phages, which have been shown to exert additive or synergistic effects in controlling bacteria. However, it is still unclear to what extent these combinatory effects are limited by rapid evolution of resistance, especially when the pathogen grows as biofilm on surfaces typical for many persistent and chronic infections. To study this, we used a microcosm system, where genetically isogenic populations of Pseudomonas aeruginosa PAO1 bacterial pathogen were exposed to a phage 14/1, gentamycin or a combination of them both in a spatially structured environment. We found that even though antibiotic and phage–antibiotic treatments were equally effective at controlling bacteria in the beginning of the experiment, combination treatment rapidly lost its efficacy in both planktonic and biofilm populations. In a mechanistic manner, this was due to rapid resistance evolution: While both antibiotic and phage selected for increased resistance on their own, phage selection correlated positively with increase in antibiotic resistance, while biofilm growth, which provided generalized resistance mechanism, was favoured most in the combination treatment. Only relatively small cost of resistance and weak evidence for coevolutionary dynamics were observed. Together, these results suggest that spatial heterogeneity can promote rapid evolution of generalized resistance mechanisms without corresponding increase in phage infectivity, which could potentially limit the effectiveness of phage–antibiotic treatments in the evolutionary timescale.

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“…It is widely known, for P. aeruginosa at least, that different nutritional cues result in altered biofilm formation, virulence, motility, and QS [46,[113][114][115][116][117]. These differences become increasingly important when factors of clinical relevance, such as virulence and antimicrobial tolerance, are altered [13,118,119]. Nutritional cues similar to those of expectorated CF sputum have been incorporated into a synthetic CF sputum media (SCFM) that approximates P. aeruginosa gene expression to that observed in expectorated CF sputum [120].…”

Section: In Vivo Conditions In Vitro Methodsmentioning

confidence: 99%

“…Conversely, chronic infections are where there is a delay in the healing process (an inability of the injured site to restore anatomical and functional integrity), consistent with the severity of the injury [9]. The presence of biofilms and their innate ability to tolerate antibiotics up to 1000 times greater than planktonic cells, is thought to delay wound restoration [10][11][12][13]. Cells assuming the biofilm phenotype are commonly observed in patients with various underlying conditions, which can be system wide in the case of immunodeficiency and diabetes, or more focused in the case of venous leg ulcers and cystic fibrosis (CF).…”

Section: Introductionmentioning

confidence: 99%

The Limitations of In Vitro Experimentation in Understanding Biofilms and Chronic Infection

Roberts

Kragh

Bjarnsholt

et al. 2015

Journal of Molecular Biology

168

153

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We have become increasingly aware that during infection, pathogenic bacteria often grow in multicellular biofilms which are often highly resistant to antibacterial strategies. In order to understand how biofilms form and contribute to infection, in vitro biofilm systems such as microtitre plate assays and flow cells, have been heavily used by many research groups around the world. Whilst these methods have greatly increased our understanding of the biology of biofilms, it is becoming increasingly apparent that many of our in vitro methods do not accurately represent in vivo conditions. Here we present a systematic review of the most widely used in vitro biofilm systems, and we discuss why they are not always representative of the in vivo biofilms found in chronic infections. We present examples of methods that will help us to bridge the gap between in vitro and in vivo biofilm work, so that our bench-side data can ultimately be used to improve bedside treatment.

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Antibiotic resistance of bacteria in biofilms

Cited by 3,937 publications

References 36 publications

In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia burgdorferi and Borrelia garinii

In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia burgdorferi and Borrelia garinii

Rapid evolution of generalized resistance mechanisms can constrain the efficacy of phage–antibiotic treatments

The Limitations of In Vitro Experimentation in Understanding Biofilms and Chronic Infection

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