Biofilms of pathogenic nontuberculous mycobacteria targeted by new therapeutic approaches
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Biofilms of pathogenic nontuberculous mycobacteria targeted by new therapeutic approaches. / Aung, Thet Tun; Yam, Joey Kuok Hoong; Lin, Shuimu; Salleh, Shuhaida Mohamed; Givskov, Michael; Liu, Shouping; Lwin, Nyein Chan; Yang, Liang; Beuerman, Roger W.
In: Antimicrobial Agents and Chemotherapy, Vol. 60, No. 1, 01.01.2016, p. 24-35.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Biofilms of pathogenic nontuberculous mycobacteria targeted by new therapeutic approaches
AU - Aung, Thet Tun
AU - Yam, Joey Kuok Hoong
AU - Lin, Shuimu
AU - Salleh, Shuhaida Mohamed
AU - Givskov, Michael
AU - Liu, Shouping
AU - Lwin, Nyein Chan
AU - Yang, Liang
AU - Beuerman, Roger W.
N1 - Publisher Copyright: Copyright © 2015 Aung et al.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84957928103&partnerID=8YFLogxK
U2 - 10.1128/AAC.01509-15
DO - 10.1128/AAC.01509-15
M3 - Journal article
C2 - 26459903
AN - SCOPUS:84957928103
VL - 60
SP - 24
EP - 35
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 1
ER -
ID: 340025806