Biofilms of Pathogenic Nontuberculous Mycobacteria Targeted by New Therapeutic Approaches

Author:

Aung Thet Tun12,Yam Joey Kuok Hoong3,Lin Shuimu1,Salleh Shuhaida Mohamed1,Givskov Michael3,Liu Shouping14,Lwin Nyein Chan1,Yang Liang23,Beuerman Roger W.145

Affiliation:

1. Singapore Eye Research Institute, Singapore

2. School of Biological Sciences, Nanyang Technological University, Singapore

3. Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore

4. SRP Neuroscience and Behavioral Disorders, Duke-NUS, Singapore

5. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Abstract

ABSTRACT Microbial infections of the cornea are potentially devastating and can result in permanent visual loss or require vision-rescuing surgery. In recent years, there has been an increasing number of reports on nontuberculous mycobacterial infections of the cornea. Challenges to the management of nontuberculous mycobacterial keratitis include delayed laboratory detection, low index of clinical suspicion, poor drug penetration, slow response to therapy, and prolonged use of antibiotic combinations. The ability of nontuberculous mycobacteria to evade the host immune response and the ability to adhere and to form biofilms on biological and synthetic substrates contribute to the issue. Therefore, there is an urgent need for new antimicrobial compounds that can overcome these problems. In this study, we evaluated the biofilm architectures for Mycobacterium chelonae and Mycobacterium fortuitum in dynamic flow cell chamber and 8-well chamber slide models. Our results showed that mycobacterial biofilms were quite resistant to conventional antibiotics. However, DNase treatment could be used to overcome biofilm resistance. Moreover, we successfully evaluated a new antimicrobial compound (AM-228) that was effective not only for planktonic mycobacterial cells but also for biofilm treatment and was compared favorably with the most successful “fourth-generation” fluoroquinolone, gatifloxacin. Finally, a new treatment strategy emerged: a combination of DNase with an antibiotic was more effective than an antibiotic alone.

Funder

Ministry of Health—Singapore

Ministry of Education—Singapore

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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