Differential Susceptibility of Mixed Polymicrobial Biofilms Involving Ocular Coccoid Bacteria (Staphylococcus aureus and S. epidermidis) and a Filamentous Fungus (Fusarium solani) on Ex Vivo Human Corneas.

Biofilms confer several advantages to the organisms associated with them, such as increased resistances to antibacterial and antifungal compounds compared to free living cells. Compared to monomicrobial biofilms involving a single microorganism, biofilms composed of microorganisms affiliated to bacterial and fungal kingdoms are predominant in nature. Despite the predominance of polymicrobial biofilms, and more so mixed polymicrobial biofilms, they are rarely studied. The objective of the current study is to evaluate the potential of ocular bacteria and a filamentous fungus to form monomicrobial and mixed polymicrobial biofilms on synthetic and natural substrates and to monitor their response to antibiotics. In this sense, we demonstrated that the ocular pathogens Staphylococcus aureus, S. epidermidis, and Fusarium solani form monomicrobial and mixed polymicrobial biofilms both on tissue culture polystyrene plates and on ex vivo human corneas from cadavers using confocal microscopy and scanning electron microscopy. Additionally, the mixed polymicrobial biofilms involving the above ocular bacteria and a filamentous fungus were less susceptible to different antibacterials and antifungals in relation to the corresponding control planktonic cells. Further, the MICs to the screened antibacterials and antifungals in polymicrobial biofilms involving a bacterium or a fungus was either increased, decreased, or unchanged compared to the corresponding individual bacterial or fungal biofilm. The results would be useful to the ophthalmologist to plan effective treatment regimens for the eye since these are common pathogens of the eye causing keratitis, endophthalmitis, conjunctivitis, etc.

Intraocular Microbiome in Diabetes and Diabetic Retinopathy: A Pilot Study.

INTRODUCTION: The objective of this study was to compare the microbiome in the aqueous humour and gut of people with diabetes mellitus (DM) with and without diabetic retinopathy (DR). METHODS: This was a prospective controlled study. The study included 17 people undergoing intraocular surgery in their naïve eyes. Stool samples were obtained in the perioperative period; aqueous humour samples of sufficient quantity were obtained in 12 people during intraocular surgery. Dietary information was obtained using a previously validated questionnaire. The gut and aqueous humour samples were assessed for microbiome using 16S rRNA gene sequencing coupled with QIIME and R software. RESULTS: Aqueous humour was analysed in 12 people: 4 each healthy controls, people with DM, and people with DR. There were minor differences at the phyla levels, but the aqueous humour microbiomes of healthy controls, DM, and DR formed three distinct clusters on heat map analysis with discriminatory genera. This genera-level clustering was more apparent for the intraocular than the gut microbiome. In people with DM and DR, we identified genera unique to the eye or the gut. There was a consistent reduction in the abundance of anti-inflammatory bacteria in people with DR than DM. CONCLUSIONS: There is a difference in intraocular and gut microbiome regardless of disease or health. Our preliminary findings indicate distinctive features of the intraocular microbiome in people with DR compared with those without it. While this distinctiveness appears more evident in aqueous humour than in the gut, it needs further confirmation with larger studies.

Unconventional avenues to decelerate diabetic retinopathy.

Diabetic retinopathy (DR) is an important microvascular complication of diabetes mellitus (DM), causing significant visual impairment worldwide. Current gold standards for retarding the progress of DR include blood sugar control and regular fundus screening. Despite these measures, the incidence and prevalence of DR and vision-threatening DR remain high. Given its slowly progressive course and long latent period, opportunities to contain or slow DR before it threatens vision must be explored. This narrative review assesses the recently described unconventional strategies to retard DR progression. These include gut-ocular flow, gene therapy, mitochondrial dysfunction-oxidative stress, stem cell therapeutics, neurodegeneration, anti-inflammatory treatments, lifestyle modification, and usage of phytochemicals. These therapies impact DR directly, while some of them also influence DM control. Most of these strategies are currently in the preclinical stage, and clinical evidence remains low. Nevertheless, our review suggests that these approaches have the potential for human use to prevent the progression of DR.

Polymicrobial biofilms of ocular bacteria and fungi on ex vivo human corneas.

Microbes residing in biofilms confer several fold higher antimicrobial resistances than their planktonic counterparts. Compared to monomicrobial biofilms, polymicrobial biofilms involving multiple bacteria, multiple fungi or both are more dominant in nature. Paradoxically, polymicrobial biofilms are less studied. In this study, ocular isolates of Staphylococcus aureus, S. epidermidis and Candida albicans, the etiological agents of several ocular infections, were used to demonstrate their potential to form mono- and polymicrobial biofilms both in vitro and on human cadaveric corneas. Quantitative (crystal violet and XTT methods) and qualitative (confocal and scanning electron microscopy) methods demonstrated that they form polymicrobial biofilms. The extent of biofilm formation was dependent on whether bacteria and fungi were incubated simultaneously or added to a preformed biofilm. Additionally, the polymicrobial biofilms exhibited increased resistance to different antimicrobials compared to planktonic cells. When the MBECs of different antibacterial and antifungal agents were monitored it was observed that the MBECs in the polymicrobial biofilms was either identical or decreased compared to the monomicrobial biofilms. The results are relevant in planning treatment strategies for the eye. This study demonstrates that ocular bacteria and fungi form polymicrobial biofilms and exhibit increase in antimicrobial resistance compared to the planktonic cells.

Evidence Suggesting the Role of Gut Dysbiosis in Diabetic Retinopathy.

Purpose: Gut dysbiosis has been identified and tested in human trials for its role in diabetes mellitus (DM). The gut-retina axis could be a potential target for retardation of diabetic retinopathy (DR), a known complication of DM. This study reviews the evidence suggesting gut dysbiosis in DR. Methods: The published literature in the past 5 years was reviewed using predetermined keywords and articles. The review intended to determine changes in gut microbiome in DR, the hypothesized mechanisms linking to the gut-retina axis, its predictive potential for progression of DR, and the possible therapeutic targets. Results: The gut microbiota of people with DM differ from those without it, and the gut microbiota of people with DR differ from those without it. The difference is more significant in the former (DM versus no DM) and less significant in the latter (DM without DR versus DM with DR). Early research has suggested mechanisms of the gut-retina axis, but these are not different from known changes in the gut microbiome of people with DM. The current evidence on the predictive value of the gut microbiome in the occurrence and progression of DR is low. Therapeutic avenues targeting the gut-retina axis include lifestyle changes, pharmacologic inhibitors, probiotics, and fecal microbiota transplantation. Conclusions: Investigating the therapeutic utility of the gut ecosystem for DM and its complications like DR is an emerging area of research. The gut-retina axis could be a target for retardation of DR but needs longitudinal regional studies adjusting for dietary habits.

Characterising the tear bacterial microbiome in young adults.

Conjunctival swabs (CS) are the major source of sampling for ocular microbiome studies, however collecting CS from the diseased eyes is difficult and painful. In this study, as an alternative to CS, a less invasive approach of tear collection was used to establish the bacterial microbiome in healthy eyes. Tear bacterial microbiome was generated from the DNA of tears (n = 24; male = 16 and female = 8) of healthy volunteers aged from 20 to 52 years. Sequencing of V3-V4 region of 16S rRNA gene was performed on the Illumina platform. Reads were processed in QIIME to assign the taxa. Statistical analysis of the tear microbiome was done in R to assess the alphadiversity and betadiversity indices. Tear microbiome was generated in all the 24 tear samples. Eight out of the top 10 predominant bacterial genera remained same in both tear and CS microbiomes, which include genera such as Corynebacterium, Staphylococcus, Streptococcus, Mycobacterium, Escherichia-Shigella, Lactobacillus, Bacillus and Acinetobacter. The similarity network analysis indicates that 144 out of 145 genera of tear cohort matched with conjunctival swabs. However, tear and CS microbiomes differed in the abundance of the predominant bacterial genera. The bacterial microbiome of tears in adults appears to be stable and is comparable with that of CS microbiome.

Gut mycobiome dysbiosis in rats showing retinal changes indicative of diabetic retinopathy.

The current study compared the gut mycobiomes of diabetic rats generated by a streptozotocin chemical challenge, diabetic rats with retinal changes and normal control rats over a period of 4 months. Sustained increase in blood sugar levels (>150 mg/dL) confirmed the induction of diabetes. Histology and immunohistochemistry were used to identify changes in the retinal tissues in the diabetic rats indicative of the animals progressing into diabetic retinopathy. Gut mycobiomes generated using faecal DNA, indicated dysbiosis at the genus level in both diabetic (DM) and diabetic rats with retinal changes (DRC) when compared with the control rats. In Tables 3-6 the specific genera that were significantly increased/decreased in DM1 and DM2 and in DRC1 and DRC2 respectively compared to the respective controls CT1-CT4 rats are listed. Further, the mycobiomes of the DM and DRC rats separated into distinct clusters following heat-map analysis of the discriminating genera. In addition, ß-diversity analysis separated the mycobiomes of DM and DRC rats from that of the control rats, but the mycobiomes of diabetic rats and diabetic rats with retinal changes showed an overlap. Based on the inferred functions of the discriminating genera in the mycobiomes, we speculated that increase in pathogenic fungi might contribute to the inflammatory status both in diabetic rats and rats showing retinal changes.

Fungi of the human eye: Culture to mycobiome.

The focus of the current review is multi-fold and compares the diversity and abundance of fungi on the ocular surface by the conventional culture-based method with the more sensitive, high throughput, culture-independent NGS method. The aim is to highlight the existence of a core ocular mycobiome and explore the transition of the ocular fungal microbiota from the normal eye to the diseased eye. PubMed, Google Scholar and Medline were used to search for publications and reviews related to cultivable fungi and the mycobiome of the normal and diseased eye. The conventional cultivable approach and the NGS approach confirm that the eye has its own mycobiome and several confounding factors (age, gender, ethnicity etc.) influence the mycobiome. Further, dysbiosis in the mycobiome appears to be associated with ocular diseases and thus impacts the health of the human eye. Considering that the mycobiome of the eye is influenced by several confounding factors and also varies with respect to the disease status of the eye there is a need to extensively explore the mycobiome under different physiological conditions, different ethnicities, geographical regions etc. Such studies would unravel the diversity and abundance of the mycobiomes and contribute to our understanding of ocular health. Research focused on ocular mycobiomes may eventually help to build a targeted and individualized treatment.

Understanding the science of fungal endophthalmitis - AIOS 2021 Sengamedu Srinivas Badrinath Endowment Lecture.

Fungal endophthalmitis is a potentially blinding condition. It is more often reported from Asia, including India. The incidence is lower than bacterial endophthalmitis. But it is relatively more challenging to treat than bacterial endophthalmitis. Many eyes may need therapeutic keratoplasty and/or evisceration. The current mainstays of treatment are vitrectomy irrespective of the presenting vision, intravitreal antifungal agents, and systemic therapy; additionally, the patients could require prolonged treatment with repeat vitreous surgeries and intravitreal injections. Difficulty in clinical diagnosis, delay in microbiological culture, and limited options of antifungal drugs make the treatment more difficult and less rewarding. Three common fungi causing endophthalmitis are Aspergillus, Fusarium, and Candida. The former two are molds, often identified in exogenous endophthalmitis, postoperative and traumatic; the latter is yeast and is more often identified in endogenous endophthalmitis. A faster diagnosis with newer molecular microbiological technologies might help institute treatment earlier than it is currently possible. A target trial using big data from different regions of the world might emulate a randomized clinical trial to design a definite treatment strategy. Given fewer antifungal drugs, one must be mindful of antifungal stewardship to prevent resistance to the existing drugs.

DNMT1 and DNMT3B gene variants and their association with endometriosis in South Indian women.

BACKGROUND: Endometriosis is a multifactorial estrogen dependent gynecological disease characterized by implantation of functional endometrial tissue at ectopic positions. Though this disease is benign, it is associated with an increased risk of malignant transformation. Epigenetic disruptions like aberrant DNA methylation, resulting changes in gene expression capacity, are important in tumor progression and malignant cellular transformation. Therefore, variation in genes involved in DNA methylation might lead to disease susceptibility. PURPOSE: To investigate the association between DNA methyl transferases (DNMT1 and DNMT3B) single nucleotide polymorphisms (SNPs) and the risk of endometriosis in South Indian women. METHODS: In the present study, we examined the genotypic and allele distribution of DNMT1 (rs10423341C/A, rs2228611G/Aandrs4804490C/A) and DNMT3B (rs1569686G/T) among the endometriosis patients (n = 150) and controls (n = 150). The genotypes were analyzed by polymerase chain reaction (PCR) and sequencing methods. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pairwise linkage disequilibrium (LD) were surveyed by Haploview Software. RESULT: Significant increase in the frequencies of DNMT1 rs10423341 (P = 0.04601), rs2228611 (P = 0.00175) and DNMT3B rs1569686 (P = 0.033) genotypes and alleles was observed in patients compared to controls. In addition, the frequency of A/A/C (P = 0.0065) haplotype was significantly high in patients. But the DNMT1 (rs4804490) SNP did not show significant association with the disease. CONCLUSION: The DNMT1 and DNMT3B polymorphism may constitute an inheritable risk factor for endometriosis in South Indian women. To the best of our knowledge there is no reported study on the association of polymorphisms in DNMT1 and DNMT3B with endometriosis risk.

Intraocular Viral Communities Associated With Post-fever Retinitis.

The virome of ocular fluids is naive. The results of this study highlight the virome in the vitreous fluid of the eye of individuals without any ocular infection and compare it with the virome of the vitreous fluid of individuals with retinitis. A total of 1,016,037 viral reads were generated from 25 vitreous fluid samples comprising control and post-fever retinitis (PFR) samples. The top 10 viral families in the vitreous fluids comprised of Myoviridae, Siphoviridae, Phycodnaviridae, Herpesviridae, Poxviridae, Iridoviridae, Podoviridae, Retroviridae, Baculoviridae, and Flaviviridae. Principal coordinate analysis and heat map analysis clearly discriminated the virome of the vitreous fluid of the controls from that of the PFR virome. The abundance of 10 viral genera increased significantly in the vitreous fluid virome of the post-fever retinitis group compared with the control group. Genus Lymphocryptovirus, comprising the human pathogen Epstein-Barr virus (EBV) that is also implicated in ocular infections was significantly abundant in eight out of the nine vitreous fluid viromes of post-fever retinitis group samples compared with the control viromes. Human viruses, such as Hepacivirus, Circovirus, and Kobuvirus, were also significantly increased in abundance in the vitreous fluid viromes of post-fever retinitis group samples compared with the control viromes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analysis and the network analysis depicted an increase in the immune response by the host in the post-fever retinitis group compared with the control group. All together, the results of the study indicate changes in the virome in the vitreous fluid of patients with the post-fever retinitis group compared to the control group.

Dysbiosis in the Gut Microbiome in Streptozotocin-Induced Diabetes Rats and Follow-Up During Retinal Changes.

Purpose: To analyze the gut bacterial microbiome of streptozotocin-induced diabetic rats and rats with retinal changes. Methods: Induction of diabetes was confirmed by an increase in blood sugar (>150 mg/dL), and the progression of diabetes with retinal changes was assessed by histology and immunohistochemistry of retinal sections. Microbiomes were generated using fecal DNA, and the V3-V4 amplicons were sequenced and analyzed by QIIME and R. Results: Dysbiosis in the gut microbiome of diabetic rats and diabetic rats with retinal changes was observed at the phylum and genus levels compared with the control rats. Heat-map analysis based on the differentially abundant genera indicated that the microbiomes of controls and diabetic rats separated into two distinct clusters. The majority of the microbiomes in diabetic rats with retinal changes also formed a distinct cluster from the control rats. ß-diversity analysis separated the microbiome of control rats from the microbiome of diabetic rats and diabetic rats with retinal changes, but the microbiomes of diabetic rats and diabetic rats with retinal changes showed an overlap. Functional analysis indicated that the enhanced inflammation in diabetic rats showing retinal changes could be ascribed to a decrease in anti-inflammatory bacteria and an increase in pathogenic and proinflammatory bacteria. Conclusions: This study showed that the gut bacterial microbiome in diabetic rats with retinal changes was different compared with control rats. The results could help develop novel therapeutics for diabetics and diabetic individuals with retinal changes.

Biofilm-Forming Potential of Ocular Fluid Staphylococcus aureus and Staphylococcus epidermidis on Ex Vivo Human Corneas from Attachment to Dispersal Phase.

The biofilm-forming potential of Staphylococcus aureus and Staphylococcus epidermidis, isolated from patients with Endophthalmitis, was monitored using glass cover slips and cadaveric corneas as substrata. Both the ocular fluid isolates exhibited biofilm-forming potential by the Congo red agar, Crystal violet and 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-(phenylamino) carbonyl-2H-tetra-zolium hydroxide (XTT) methods. Confocal microscopy demonstrated that the thickness of the biofilm increased from 4-120 h of biofilm formation. Scanning electron microscopic studies indicated that the biofilms grown on cover slips and ex vivo corneas of both the isolates go through an adhesion phase at 4 h followed by multilayer clumping of cells with intercellular connections and copious amounts of extracellular polymeric substance. Clumps subsequently formed columns and eventually single cells were visible indicative of dispersal phase. Biofilm formation was more rapid when the cornea was used as a substratum. In the biofilms grown on corneas, clumping of cells, formation of 3D structures and final appearance of single cells indicative of dispersal phase occurred by 48 h compared to 96-120 h when biofilms were grown on cover slips. In the biofilm phase, both were several-fold more resistant to antibiotics compared to planktonic cells. This is the first study on biofilm forming potential of ocular fluid S. aureus and S. epidermidis on cadaveric cornea, from attachment to dispersal phase of biofilm formation.

Alterations in the gut bacterial microbiome in people with type 2 diabetes mellitus and diabetic retinopathy.

Gut bacterial microbiome dysbiosis in type 2 Diabetes Mellitus (T2DM) has been reported, but such an association with Diabetic Retinopathy (DR) is not known. We explored possible link between gut bacterial microbiome dysbiosis and DR. Using fecal samples of healthy controls (HC) and people with T2DM with/without DR, gut bacterial communities were analysed using 16S rRNA gene sequencing and data analysed using QIIME and R software. Dysbiosis in the gut microbiomes, at phyla and genera level, was observed in people with T2DM and DR compared to HC. People with DR exhibited greater discrimination from HC. Microbiomes of people with T2DM and DR were also significantly different. Both DM and DR microbiomes showed a decrease in anti-inflammatory, probiotic and other bacteria that could be pathogenic, compared to HC, and the observed change was more pronounced in people with DR. This is the first report demonstrating dysbiosis in the gut microbiome (alteration in the diversity and abundance at the phyla and genera level) in people with DR compared to HC. Such studies would help in developing novel and targeted therapies to improve treatment of DR.

Microbes of the human eye: Microbiome, antimicrobial resistance and biofilm formation.

BACKGROUND: The review focuses on the bacteria associated with the human eye using the dual approach of detecting cultivable bacteria and the total microbiome using next generation sequencing. The purpose of this review was to highlight the connection between antimicrobial resistance and biofilm formation in ocular bacteria. METHODS: Pubmed was used as the source to catalogue culturable bacteria and ocular microbiomes associated with the normal eyes and those with ocular diseases, to ascertain the emergence of anti-microbial resistance with special reference to biofilm formation. RESULTS: This review highlights the genetic strategies used by microorganisms to evade the lethal effects of anti-microbial agents by tracing the connections between candidate genes and biofilm formation. CONCLUSION: The eye has its own microbiome which needs to be extensively studied under different physiological conditions; data on eye microbiomes of people from different ethnicities, geographical regions etc. are also needed to understand how these microbiomes affect ocular health.

A systematic review of gut microbiome and ocular inflammatory diseases: Are they associated?

The primary focus of this review was to establish the possible association of dysbiotic changes in the gut bacterial microbiomes with both intestinal and extra-intestinal diseases with emphasis on ocular diseases such as bacterial keratitis, fungal keratitis, uveitis, age-related macular degeneration, and ocular mucosal diseases. For this particular purpose, a systematic search was conducted using PubMed and Google Scholar for publications related to gut microbiome and human health (using the keywords: gut microbiome, ocular disease, dysbiosis, keratitis, uveitis, and AMD). The predictions are that microbiome studies would help to unravel dysbiotic changes in the gut bacterial microbiome at the taxonomic and functional level and thus form the basis to mitigate inflammatory diseases of the eye by using nutritional supplements or fecal microbiota transplantation.

Alterations in the conjunctival surface bacterial microbiome in bacterial keratitis patients.

Microbial keratitis is an infectious disease of the eye, in which the cornea is inflamed. Under severe conditions, keratitis can lead to significant loss of vision and enucleation of the eye. Ocular trauma is the major risk factor causing keratitis and microorganisms viz., bacteria, fungi, viruses are the causative agents. The current study characterized the conjunctival bacterial microbiomes of healthy individuals and individuals with bacterial keratitis (BK) and assessed whether ocular microbiome dysbiosis is prevalent in BK patients. Ocular bacterial microbiomes were generated from the conjunctival swabs of healthy controls (HC-SW) and conjunctival swabs (BK-SW) and corneal scrapings (BK-CR) of BK patients using V3-V4 amplicon sequencing and data analysed using QIIME and R software. The Alpha diversity indices, diversity and abundance of different phyla and genera, heat map analysis, NMDS plots and inferred functional pathway analysis clearly discriminated the bacterial microbiomes of conjunctival swabs of healthy controls from that of BK patients. Preponderance of negative interactions in the hub genera were observed in BK-CR and BK-SW compared to HC-SW. In addition, a consistent increase in the abundance of pathogenic bacteria, as inferred from published literature, was observed in the conjunctiva of BK patients compared to HC and this may be related to causing or exacerbating ocular surface inflammation. This is the first study demonstrating dysbiosis in the ocular bacterial microbiome of conjunctiva of bacterial keratitis patients compared to the eye of healthy controls. The bacterial microbiome associated with the corneal scrapings of keratitis individuals is also described for the first time.

Gut mycobiomes are altered in people with type 2 Diabetes Mellitus and Diabetic Retinopathy.

Studies have documented dysbiosis in the gut mycobiome in people with Type 2 diabetes mellitus (T2DM). However, it is not known whether dysbiosis in the gut mycobiome of T2DM patients would be reflected in people with diabetic retinopathy (DR) and if so, is the observed mycobiome dysbiosis similar in people with T2DM and DR. Gut mycobiomes were generated from healthy controls (HC), people with T2DM and people with DR through Illumina sequencing of ITS2 region. Data were analysed using QIIME and R software. Dysbiotic changes were observed in people with T2DM and DR compared to HC at the phyla and genera level. Mycobiomes of HC, T2DM and DR could be discriminated by heat map analysis, Beta diversity analysis and LEfSE analysis. Spearman correlation of fungal genera indicated more negative correlation in HC compared to T2DM and DR mycobiomes. This study demonstrates dysbiosis in the gut mycobiomes in people with T2DM and DR compared to HC. These differences were significant both at the phyla and genera level between people with T2DM and DR as well. Such studies on mycobiomes may provide new insights and directions to identification of specific fungi associated with T2DM and DR and help developing novel therapies for Diabetes Mellitus and DR.

Mycobiome changes in the vitreous of post fever retinitis patients.

Fungi have been associated with various diseases of the eye like keratitis, uveitis and endophthalmitis. Despite this fact, fungal microbiome (mycobiome) studies compared to the bacterial microbiome studies have remained neglected. In the present study, using metagenomic sequencing, the mycobiomes of the vitreous of healthy control individuals (VC, n = 15) and individuals with post fever retinitis + non-PFR uveitis (PFR+, n = 9) were analysed and compared. The results indicated that Ascomycota was the most predominant phylum in both VC and PFR+ groups. Further, at the genera level it was observed that the abundance of 17 fungal genera were significantly different in post fever retinitis (PFR, n = 6) group compared to control group. Of these 17 genera, it was observed that 14 genera were relatively more abundant in PFR group and the remaining 3 genera in the VC group. Genus Saccharomyces, a commensal of the gut and skin, was predominantly present in the vitreous of both the cohorts, however it was significantly less abundant in PFR group. Further, significant increase in the genera that have a pathogenic interaction with the host were observed in PFR group. On the whole the mycobiome in both the groups differed significantly and formed two distinct clusters in the heatmap and Principal co-ordinate analysis. These results demonstrate significant changes in the mycobiome from the vitreous of post fever retinitis patients compared to healthy controls thus implying that dysbiotic changes in the fungal vitreous microbiome are associated with PFR.

Association of genetic variations in phosphatase and tensin homolog (PTEN) gene with polycystic ovary syndrome in South Indian women: a case control study.

PURPOSE: The purpose of the study was to investigate the association between gene phosphate and tensin homolog (PTEN) single nucleotide polymorphisms (SNPs) and risk of developing polycystic ovary syndrome (PCOS) in South Indian women. PTEN is one of the most important tumor suppressor genes that regulate cell proliferation, migration, and death. It is also involved in the maintenance of genome stability. PCOS is one of the most common endocrine disorders among women of reproductive age. It is a heterogeneous syndrome characterized by abnormal reproductive cycles, irregular ovulation, hormonal imbalance, hyperandrogenism, acne and hirsutism. RESEARCH QUESTION: What is the association status of PTEN SNPs with PCOS? METHODS: A total of 240 subjects were recruited in this case-control study comprising 110 patients with PCOS and 130 individuals without PCOS. All the subjects were of South Indian origin. The genotyping of PTEN SNPs (rs1903858 A/G, rs185262832G/A and rs10490920T/C) was carried out on DNA from subjects by polymerase chain reaction (PCR) and sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pairwise linkage disequilibrium (LD) were surveyed by Haploview Software. RESULTS: Our results showed significant increase in the frequencies of rs1903858 A/G (P = 0.0016), rs185262832 G/A (P = 0.0122) and rs10490920 T/C (P = 0.0234) genotypes and alleles in cases compared to controls. CONCLUSION: The PTEN (rs1903858A/G, rs185262832G/A and rs10490920T/C) gene polymorphisms may constitute an inheritable risk factor for PCOS in South Indian women.