Antimicrobial resistance, respiratory tract infections and role of biofilms in lung infections in cystic fibrosis patients

Ciofu, Oana; Tolker‐Nielsen, Tim; Jensen, Peter Østrup; Wang, Hengzhuang; Høiby, Niels

doi:10.1016/j.addr.2014.11.017

Cited by 275 publications

(352 citation statements)

References 244 publications

(277 reference statements)

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“…Our collective evidence indicates that PQS is the AQ signal associated with the most severe stress response and swarming repression upon tobramycin exposure. The spatial partitioning of PQS to the regions proximal to the highest tobramycin concentrations could serve to protect pre-biofilm communities from the deleterious effects of tobramycin, to condition swarms to antimicrobial stress, or be linked to the role of PQS in cell death and biofilm formation (10,(20)(21)(22)24,45). In response to tobramycin, AQNOs were distributed throughout the swarm, which leads us to conclude that these molecules act at a community-wide scale.…”

Section: Discussionmentioning

confidence: 92%

“…Planktonic cells are generally sensitive to antibiotics, whereas surface attached biofilms and swarming communities display increased survival and resistance (3,(8)(9)(10)(11). Therefore, it is imperative to understand how bacterial communities coordinate colonization of new surfaces and how this helps them endure the stress of traditional antibiotics.…”

Section: Introductionmentioning

confidence: 99%

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Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms

Morales-Soto¹,

Dunham

Baig

et al. 2018

Journal of Biological Chemistry

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There is a general lack of understanding about how communities of bacteria respond to exogenous toxins such as antibiotics. Most of our understanding of community-level stress responses comes from the study of stationary biofilm communities. Although several community behaviors and production of specific biomolecules affecting biofilm development and associated behavior have been described for Pseudomonas aeruginosa and other bacteria, we have little appreciation for the production and dispersal of secreted metabolites within the 2D and 3D spaces they occupy as they colonize, spread, and grow on surfaces. Here we specifically studied the phenotypic responses and spatial variability of alkyl quinolones, including the Pseudomonas quinolone signal (PQS) and members of the alkyl hydroxyquinoline (AQNO) subclass, in P. aeruginosa plateassay swarming communities. We found that PQS production was not a universal signaling response to antibiotics as tobramycin elicited an alkyl quinolone response while carbenicillin did not. We also found that PQS and AQNO profiles in response to tobramycin were markedly distinct and influenced these swarms on different spatial scales. The distribution of alkyl quinolones varied by several orders of magnitude within the same swarm. At some tobramycin exposures, P. aeruginosa swarms produced alkyl quinolones in the range of 150 µM PQS and 400 µM AQNO that accumulated as aggregates.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms

Morales-Soto¹,

Dunham

Baig

et al. 2018

Journal of Biological Chemistry

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“…Maybe this could be explained by the indiscriminate use of anti-microbials for home therapy, because in Bulgaria carbapenems, can be used only during hospital stay. Additionally, it is possible that anaerobic cultures and biofilms generated in vitro do not accurately reflect the hostile microenvironment of lungs with CF and/or that the concentrations of antibiotics used according to the consensus guidelines may not reflect the concentrations found in CF airway mucus and thus may not be effective [13].…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial susceptibility of Pseudomonas aeruginosa before and after initiation of inhaled tobramycin in Bulgaria

Petrova

Miteva

Lazova

et al. 2016

J Infect Dev Ctries

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Introduction: In aim to achieve better infection control and possible eradication of the pathogens involved in chronic infections of patients with cystic fibrosis (CF) scientists have developed a new way to administer antimicrobials -inhalation. The first and so far the only available inhalable antimicrobial in Bulgaria is inhaled tobramycin (TOBI), introduced in 2009.We aimed to evaluate the antimicrobial susceptibility of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients before and after initiation of TOBI in the regular treatment regimen. Methodology: We have determined the minimal inhibitory concentration (MIC) of 17 antimicrobials by the E-test (LIOFILCHEM) in sputa samples of 118 CF patients for the period of 2005-2014. The results were interpreted according to the annual Clinical and Laboratory Standards Institute guidelines. Results: In the sputa of 70 patients a total of 102 P. aeruginosa isolates were found. Sixty-eight out of 102 (66.7%) were susceptible to all studied antimicrobials. We divided the isolates in two chronological groups: those collected before the introduction of TOBI as a regular treatment in 2009 and those collected after 2009. A significant reduction (p < 0,001-0,02) in susceptibility for the strains after 2009 was noted towards piperacillin (100% vs 50%), ceftazidime (100% / 77.3%), cefepime (97.9% / 68.2%), amikacin (100% / 63.6%), gentamicin (95.7% / 40.9%), tobramycin (93.6% / 59.1%) and ciprofloxacin (93.6% / 45.5%). Conclusion: The introduction of inhaled tobramycin as a regular therapy for CF patients in Bulgaria lead to a significant change in antimicrobial susceptibility of CF P. aeruginosa.

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“…The organization, composition and dynamic of the biofilm community confer to the cells protection against threats from the environment, such as natural predators or exposure to harmful substances (Chiang et al, 2012;Klebensberger et al, 2009;Malone et al, 2010;Mishra et al, 2012;Tseng et al, 2013). While this mode of life appears to be beneficial for the bacterial community, it is the cause of persistent infections in medical settings and fouling problems in various industrial settings (Ciofu et al, 2015;Costerton et al, 1999;Dosler & Karaaslan, 2014;Flemming, 2002;Hill et al, 2005). In clinical settings, bacterial biofilms are difficult if not impossible to eradicate because of their tolerance towards conventional antibiotics and the host immune system (Ciofu et al, 2015;Costerton et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…While this mode of life appears to be beneficial for the bacterial community, it is the cause of persistent infections in medical settings and fouling problems in various industrial settings (Ciofu et al, 2015;Costerton et al, 1999;Dosler & Karaaslan, 2014;Flemming, 2002;Hill et al, 2005). In clinical settings, bacterial biofilms are difficult if not impossible to eradicate because of their tolerance towards conventional antibiotics and the host immune system (Ciofu et al, 2015;Costerton et al, 1999). They are responsible for diverse chronic infections and the cause of morbidity and mortality (FloresMireles et al, 2015;Mayer-Hamblett et al, 2014;Wenzel, 2007).…”

Section: Introductionmentioning

confidence: 99%

The anti-cancerous drug doxorubicin decreases the c-di-GMP content in Pseudomonas aeruginosa but promotes biofilm formation

et al. 2016

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Current antibiotic treatments are insufficient in eradicating bacterial biofilms, which represent the primary cause of chronic bacterial infections. Thus, there is an urgent need for new strategies to eradicate biofilm infections. The second messenger c-di-GMP is a positive regulator of biofilm formation in many clinically relevant bacteria. It is hypothesized that drugs lowering the intracellular level of c-di-GMP will force biofilm bacteria into a more treatable planktonic lifestyle. To identify compounds capable of lowering c-di-GMP levels in Pseudomonas aeruginosa, we screened 5000 compounds for their potential c-di-GMP-lowering effect using a recently developed c-di-GMP biosensor strain. Our screen identified the anti-cancerous drug doxorubicin as a potent c-di-GMP inhibitor. In addition, the drug decreased the transcription of many biofilm-related genes. However, despite its effect on the c-di-GMP content in P. aeruginosa, doxorubicin was unable to inhibit biofilm formation or disperse established biofilms. On the contrary, the drug was found to promote P. aeruginosa biofilm formation, possibly through release of extracellular DNA from a subpopulation of killed bacteria. Our findings emphasize that lowering of the c-di-GMP content in bacteria might not be sufficient to mediate biofilm inhibition or dispersal.

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Antimicrobial resistance, respiratory tract infections and role of biofilms in lung infections in cystic fibrosis patients

Cited by 275 publications

References 244 publications

Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms

Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms

Antimicrobial susceptibility of Pseudomonas aeruginosa before and after initiation of inhaled tobramycin in Bulgaria

The anti-cancerous drug doxorubicin decreases the c-di-GMP content in Pseudomonas aeruginosa but promotes biofilm formation

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