Mitochondrial mutations associated with aminoglycoside ototoxicity and hearing loss susceptibility identified by meta-analysis

Wu, Jing; Zeng, Hao; Fu, Denggang; Na, Hei; Zhang, Bin; Aifen, Zhou; Hu, Xijiang; Cong, Yao; Dong, Yuchen; Ring, Huijun Z.; Ring, Brian Z.

doi:10.1136/jmedgenet-2014-102753

Cited by 33 publications

(23 citation statements)

References 57 publications

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“…However, P. aeruginosa has been demonstrated to be resistant to a wide variety of antibiotics including β lactams (penicillins, cephalosporins, and carbapenems), fluoroquinolones (ciprofloxacin), polymyxins and macrolides (erythromycin and azithromycin) (Nordmann and Guibert, 1998; Livermore, 2002; Walsh et al, 2003; Jang and Park, 2004; Poole, 2004, 2011; Saunders J. et al, 2011; Morita et al, 2014; Mittal et al, 2015). P. aeruginosa exhibits some degree of sensitivity to aminoglycosides but this class of antibiotics has significant ototoxicity and is not recommended for the treatment of CSOM (Black et al, 2004; Jing et al, 2015; Koo et al, 2015; Leis et al, 2015). A better knowledge of the interaction of pathogens with immune cells will provide new opportunities to design effective novel therapeutic strategies against CSOM.…”

Section: Discussionmentioning

confidence: 99%

Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

et al. 2016

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Otitis media (OM) is a broad term describing a group of infectious and inflammatory disorders of the middle ear. Despite antibiotic therapy, acute OM can progress to chronic suppurative otitis media (CSOM) characterized by ear drum perforation and purulent discharge. Pseudomonas aeruginosa is the most common pathogen associated with CSOM. Although, macrophages play an important role in innate immune responses but their role in the pathogenesis of P. aeruginosa-induced CSOM is not known. The objective of this study is to examine the interaction of P. aeruginosa with primary macrophages. We observed that P. aeruginosa enters and multiplies inside human and mouse primary macrophages. This bacterial entry in macrophages requires both microtubule and actin dependent processes. Transmission electron microscopy demonstrated that P. aeruginosa was present in membrane bound vesicles inside macrophages. Interestingly, deletion of oprF expression in P. aeruginosa abrogates its ability to survive inside macrophages. Our results suggest that otopathogenic P. aeruginosa entry and survival inside macrophages is OprF-dependent. The survival of bacteria inside macrophages will lead to evasion of killing and this lack of pathogen clearance by phagocytes contributes to the persistence of infection in CSOM. Understanding host–pathogen interaction will provide novel avenues to design effective treatment modalities against OM.

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Section: Discussionmentioning

confidence: 99%

Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

et al. 2016

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“…Indeed, genetic variants can predispose to hearing loss. Mitochondrial DNA mutations have been linked to sensitivity to aminoglycosides and have also been associated with hearing loss in the absence of exposure to aminoglycosides [ 48 ]. Screening for genetic variants associated with hearing loss could identify patients at risk, but the opportunity for prevention may be limited as gentamicin is often prescribed on the first day of life for suspected early-onset sepsis [ 37 , 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Gentamicin Exposure and Sensorineural Hearing Loss in Preterm Infants

et al. 2016

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ObjectiveTo evaluate the impact of gentamicin exposure on sensorineural hearing loss (SNHL) in very low birth weight (VLBW) infants.MethodsExposure to gentamicin was determined in infants born between 1993 and 2010 at a gestational age < 32 weeks and/or with a birthweight < 1500 g, who presented with SNHL during the first 5 years of life. For each case, we selected two controls matched for gender, gestational age, birthweight, and year of birth.ResultsWe identified 25 infants affected by SNHL, leading to an incidence of SNHL of 1.58% in our population of VLBW infants. The proportion of infants treated with gentamicin was 76% in the study group and 70% in controls (p = 0.78). The total cumulated dose of gentamicin administered did not differ between the study group (median 10.2 mg/kg, Q1-Q3 1.6–13.2) and the control group (median 7.9 mg/kg, Q1-Q3 0–12.8, p = 0.47). The median duration of gentamicin treatment was 3 days both in the study group and the control group (p = 0.58). Maximum predicted trough serum levels of gentamicin, cumulative area under the curve and gentamicin clearance were not different between cases and controls.ConclusionThe impact of gentamicin on SNHL can be minimized with treatments of short duration, monitoring of blood levels and dose adjustment.

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“…It is well known that in individuals with aminoglycoside-induced ototoxicity, mitochondrial genome mutations, for example, m.1555A>G and m.1494C>T, are often detected. 78 , 79 , 91 …”

Section: Syndromes Of Mitochondrial Cytopathiesmentioning

confidence: 99%

Mitochondrial diseases caused by mtDNA mutations: a mini-review

Рыжкова

Sazonova

Sinyov

et al. 2018

TCRM

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There are several types of mitochondrial cytopathies, which cause a set of disorders, arise as a result of mitochondria’s failure. Mitochondria’s functional disruption leads to development of physical, growing and cognitive disabilities and includes multiple organ pathologies, essentially disturbing the nervous and muscular systems. The origins of mitochondrial cytopathies are mutations in genes of nuclear DNA encoding mitochondrial proteins or in mitochondrial DNA. Nowadays, numerous mtDNA mutations significant to the appearance and progress of pathologies in humans are detected. In this mini-review, we accent on the mitochondrial cytopathies related to mutations of mtDNA. As well known, there are definite set of symptoms of mitochondrial cytopathies distinguishing or similar for different syndromes. The present article contains data about mutations linked with cytopathies that facilitate diagnosis of different syndromes by using genetic analysis methods. In addition, for every individual, more effective therapeutic approach could be developed after wide-range mutant background analysis of mitochondrial genome.

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Mitochondrial mutations associated with aminoglycoside ototoxicity and hearing loss susceptibility identified by meta-analysis

Cited by 33 publications

References 57 publications

Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

Otopathogenic Pseudomonas aeruginosa Enters and Survives Inside Macrophages

Gentamicin Exposure and Sensorineural Hearing Loss in Preterm Infants

Mitochondrial diseases caused by mtDNA mutations: a mini-review

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