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Cystic fibrosis infection and biofilm busters
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Jennifer Fiegel, Sachin Gharse
Bacteriophages (or phages) are viruses that infect bacteria, where they replicate to a high density and burst the bacterial cell (a process called amplification). Phage therapy represents a potential alterative treatment as antibiotic-resistant bacteria and biofilms do not present a challenge to phage (83). Pearl et al. (2008) demonstrated that phages remain alive within persister cells, then replicate when the persisters become active (66). Phages diffuse readily through biofilm matrices (67), expressing depolymerizing enzymes that degrade biofilm matrices and/or inducing the bacteria to express enzymes to further biofilm degradation (52,84). In mice with chronic P. aeruginosa infections, treatment with phages 24 or 48 hours post-infection resulted in complete clearance of P. aeruginosa from the lungs. After 6 days of infection, complete clearance was observed in 70% of the mice, with significant reduction in bacterial load in the remaining animals (68).
Biofilm Persisters
Published in Chaminda Jayampath Seneviratne, Microbial Biofilms, 2017
Peng Li, Chaminda Jayampath Seneviratne, Lijian Jin
The existence of persister cells in a wide variety of microbial subpopulations is becoming increasingly evident from recent studies. More and more treatment strategies end in failure because of the prevalence of persisters. Hence, this phenomenon of resistance can render therapeutic regimens ineffective unless they are effectively targeted. An expanding plethora of research in this direction is therefore warranted to necessitate both an understanding of the molecular mechanisms behind persister resistance and an efficient combative strategy against persisters. Altogether, persister cell biology has become one of the fascinating biofilm research areas of recent times, with a potential gold mine of understanding waiting to be uncovered.
Advances in the design of combination therapies for the treatment of tuberculosis
Published in Expert Opinion on Drug Discovery, 2023
Jonah Larkins-Ford, Bree B. Aldridge
Decreased resistance development was clinically demonstrated during the early trials using S and PAS. In one early study, S monotherapy resulted in 20% of patients developing resistance [2] and the randomized control trials from the Medical Research Council (MRC) in the United Kingdom found streptomycin resistance in 70% of cases [2,59,60]. In contrast, the MRC studies found that streptomycin resistance could be detected in 41% of cases receiving both S and PAS and was found in as few as 9% of cases when PAS was administered every 3 days [2,59,60]. These early studies demonstrated the necessity of combination therapy to prevent resistance development. Therefore, it is not surprising that the development of short-course therapy for TB treatment utilizes at least three drugs. Clinical studies have demonstrated that we require combination therapy to bet-hedge treatment against variation in access and susceptibility to Mtb that resides in different lesions. Combination therapies should therefore include drugs that coordinate to rapidly reduce bacterial burden and then sterilize persister cells.
Synergistic antimicrobial combination of carvacrol and thymol impairs single and mixed-species biofilms of Candida albicans and Staphylococcus epidermidis
Published in Biofouling, 2020
Thirukannamangai Krishnan Swetha, Arumugam Vikraman, Chari Nithya, Nagaiah Hari Prasath, Shunmugiah Karutha Pandian
The antibiotic resistance and persistence of biofilm-assisted infections have been linked to the presence of persister cells. These cells are a subset of cells in a normal biofilm, which remain dormant and tolerate even high doses of antibiotics (Bigger 1944; LaFleur et al. 2006; Shapiro et al. 2011). The efficacy of the C + T combination in killing persister cells was assessed. A previous study demonstrated the lethality of a 2× concentration of an antimicrobial peptide SAAP-148 on persister cells in S. aureus biofilms within 2 h of treatment (de Breij et al. 2018). Presently, 2× and 4× the ESCs of C + T completely eradicated persister cells in both single- and mixed-species biofilms within 2h of treatment. The findings indicate the potential value of C + T to treat latent infections.
A systematic review of implications, mechanisms, and stability of in vivo emergent resistance to colistin and tigecycline in Acinetobacter baumannii
Published in Journal of Chemotherapy, 2020
Rapid emergence of colistin resistance from a heteroresistant population during treatment may allow A. baumannii to survive under antibiotic pressure. To prevent emergence of resistance during treatment several combination antimicrobial regimens have been proposed5,6,52–55 but without improvement in clinical outcomes in most studies.2,52–57 When antibiotic pressure ceases the fitter and more virulent ancestral susceptible strain may re-emerge,26 potentially resulting in re-infection in the same patient or transmission to other patients. The development of persister cells (viable but non-dividing cells that can survive lethal doses of antibiotics and are able to re-emerge after cessation of antibiotic pressure) during treatment may explain the persistence and re-emergence of susceptible strains.58 Of note is that colistin heteroresistance is likely to be missed by methods such as Vitek 2 or E-test26,36,51 and may even be missed with broth microdilution.33,59 Therefore, the true prevalence of in vivo colistin resistance may be underestimated and its impact under-recognized.