Aspergillus flavus induced alterations in tear protein profile reveal pathogen-induced host response to fungal infection

Kandhavelu, Jeyalakshmi; Demonte, Naveen Luke; Namperumalsamy, Venkatesh Prajna; Lalitha, Prajna; Thangavel, Chitra; Jayapal, Jeya Maheshwari; Dharmalingam, Kuppamuthu

doi:10.1016/j.jprot.2016.10.009

Cited by 28 publications

(36 citation statements)

References 42 publications

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“…In our case series, Patient 12 was treated twice with tectonic keratoplasty with no better visual acuity . In endophthalmitis cases, antifungal treatment including intravitreal VCZ or AMB.…”

Section: Discussionmentioning

confidence: 88%

Epidemiology of Aspergillus species causing keratitis in Mexico

Al‐Hatmi

Castro

Hoog

et al. 2018

Mycoses

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Summary Background The incidence of fungal keratitis has increased in recent years. While the epidemiology and clinical roles of various Candida and Fusarium species have been relatively well‐identified in infections of the eye, data regarding keratitis caused by Aspergillus species are scant. Accurate and rapid diagnosis is important for successful management of this infection. Objectives To present the first molecular epidemiological data from Mexico during a 4‐year period of cases admitted with Aspergillus keratitis to a tertiary care eye institution in Mexico City. Patients/Methods A total of 25 cases of keratitis were included in the study. Aspergillus isolates were identified by sequencing the calmodulin gene. Antifungal susceptibility was tested according to CLSI. Results The aetiological agents belonged to Aspergillus flavus (n = 13), Aspergillus effusus (n = 1), Aspergillus tamarii (n = 4), Aspergillus sydowii (n = 1), Aspergillus protuberus (n = 3) and Aspergillus terreus (n = 3). All strains had low minimum inhibitory concentrations (MICs) of itraconazole and voriconazole (VCZ). Amphotericin B and natamycin showed moderate elevated MICs. Conclusions Early diagnosis and application of topical VCZ 1% were associated with good outcome. Monitoring of local epidemiological data plays an important role in clinical practice.

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Section: Discussionmentioning

confidence: 88%

Epidemiology of Aspergillus species causing keratitis in Mexico

Al‐Hatmi

Castro

Hoog

et al. 2018

Mycoses

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“…Our previous studies have shown the presence of several complement proteins in the tear proteome of keratitis patients (Kandhavelu et al, 2017). We also showed the presence of negative regulators namely, CFH, vitronectin and clusterin (inhibitors of the membrane attack complex), and lactoferrin (acts on soluble C3) (Kandhavelu et al, 2017). Previous reports clearly showed lactoferrin, an abundant protein found in human tear, inhibit the classical pathway of complement cascade but not the alternative pathway (Kievjts and Kijlstra, 1985).…”

Section: Introductionmentioning

confidence: 59%

“…These proteins in the tear are shown to be active functionally. Our previous studies have shown the presence of several complement proteins in the tear proteome of keratitis patients (Kandhavelu et al, 2017). We also showed the presence of negative regulators namely, CFH, vitronectin and clusterin (inhibitors of the membrane attack complex), and lactoferrin (acts on soluble C3) (Kandhavelu et al, 2017).…”

Section: Introductionmentioning

confidence: 66%

“…Mycotic keratitis is more widespread in India and other tropical parts of the world (Erie et al, 1993;Mohammed et al, 2019b). Tear film plays a crucial role in immune defense against the invading microbes and the presence of most of the proteins involved in the alternate pathway of complement cascade has been demonstrated in patient tear (Ananthi et al, 2013;Kandhavelu et al, 2017). Previous studies showed the presence of several innate immune response associated proteins such as NET proteins, wound healing proteins and complement proteins in patient tear (Kandhavelu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Tear film plays a crucial role in immune defense against the invading microbes and the presence of most of the proteins involved in the alternate pathway of complement cascade has been demonstrated in patient tear (Ananthi et al, 2013;Kandhavelu et al, 2017). Previous studies showed the presence of several innate immune response associated proteins such as NET proteins, wound healing proteins and complement proteins in patient tear (Kandhavelu et al, 2017). Activation of the alternate pathway requires appropriate foreign surface for binding of the complement proteins and their subsequent activation.…”

Section: Introductionmentioning

confidence: 99%

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Local Activation of the Alternative Pathway of Complement System in Mycotic Keratitis Patient Tear

Mohammed

Krishnan

Amrathlal

et al. 2020

Front. Cell. Infect. Microbiol.

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Aspergillus flavus and Fusarium solani are the predominant causative agents of mycotic keratitis in the tropical part of the world. Tear proteins play a major role in the innate immune response against these fungal infections as has been shown by the presence of complement proteins and neutrophil extracellular trap proteins in keratitis patients tear. In this study, we established the presence of the components of the alternate pathway of complement system and their functional state in the tear film of mycotic keratitis patients. The complement proteins namely, C3 and CFH were found only in the open-eye tear of patients but not in control individuals. In vitro analysis showed binding of purified C3b and CFH to fungal spores, which confirmed that the spores can provide a foreign surface for forming the complement complex. Analysis of spore bound tear proteins by mass spectrometry exhibited the presence of known proteins of the alternate pathway complement cascade in keratitis patient tear. Hemolytic assay using rabbit RBC confirmed the presence of a functional alternate pathway of complement cascade in the tear proteome of the patients. The presence of negative regulators, CFH and CFI, in the patient tear indicate that the complement activity is tightly regulated during fungal infection. Mass spectrometry data show vitronectin and clusterin, two known inhibitors of the membrane attack complex only in the patient tear. These data demonstrate the activation of the alternate pathway of complement cascade during the early stages of infection. Interestingly, the production of multiple negative regulators of complement cascade implies the pathogen can effectively evade the host complement system during infection.

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Milestones in Medical Mycology in India

Gugnani

2021

Progress in Mycology

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Aspergillus flavus induced alterations in tear protein profile reveal pathogen-induced host response to fungal infection

Cited by 28 publications

References 42 publications

Epidemiology of Aspergillus species causing keratitis in Mexico

Epidemiology of Aspergillus species causing keratitis in Mexico

Local Activation of the Alternative Pathway of Complement System in Mycotic Keratitis Patient Tear

Milestones in Medical Mycology in India

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