scholarly journals Candida glabrata: Pathogenicity and Resistance Mechanisms for Adaptation and Survival

2021 ◽  
Vol 7 (8) ◽  
pp. 667
Author(s):  
Yahaya Hassan ◽  
Shu Yih Chew ◽  
Leslie Thian Lung Than
Keyword(s):  
Virulence Factors ◽  
Candida Glabrata ◽  
High Stress ◽  
Hydrolytic Enzymes ◽  
The Elderly ◽  
Resistance Mechanisms ◽  
Antifungal Drugs ◽  
Diabetic Patients ◽  
Susceptible Host ◽  
Development Of Resistance

Candida glabrata is a yeast of increasing medical relevance, particularly in critically ill patients. It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans. The attributed higher incidence is primarily due to an increase in the acquired immunodeficiency syndrome (AIDS) population, cancer, and diabetic patients. The elderly population and the frequent use of indwelling medical devices are also predisposing factors. This work aimed to review various virulence factors that facilitate the survival of pathogenic C. glabrata in IC. The available published research articles related to the pathogenicity of C. glabrata were retrieved and reviewed from four credible databases, mainly Google Scholar, ScienceDirect, PubMed, and Scopus. The articles highlighted many virulence factors associated with pathogenicity in C. glabrata, including adherence to susceptible host surfaces, evading host defences, replicative ageing, and producing hydrolytic enzymes (e.g., phospholipases, proteases, and haemolysins). The factors facilitate infection initiation. Other virulent factors include iron regulation and genetic mutations. Accordingly, biofilm production, tolerance to high-stress environments, resistance to neutrophil killings, and development of resistance to antifungal drugs, notably to fluconazole and other azole derivatives, were reported. The review provided evident pathogenic mechanisms and antifungal resistance associated with C. glabrata in ensuring its sustenance and survival.

scholarly journals Candida glabrata: Adopting Pathogenicity and Resistant Mechanisms for Survival

2021 ◽  
Author(s):  
Yahaya Hassan ◽  
Shu Yih Chew ◽  
Leslie Thian Lung Than
Keyword(s):  
Virulence Factors ◽  
Candida Glabrata ◽  
High Stress ◽  
Hydrolytic Enzymes ◽  
The Elderly ◽  
Susceptible Host ◽  
Development Of Resistance ◽  
Frequent Use ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

Candida glabrata is a yeast of increasing medical relevance, particularly in critically ill patients. It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans. The attributed higher incidence is primarily due to an increase in the acquired immunodeficiency syndrome (AIDS) population, cancer, and diabetes patients. The elderly population and the frequent use of indwelling medical devices are also predisposing factors. The work aimed to review various virulence factors that facilitate the survival of pathogenic C. glabrata in IC. The available published research articles related to the pathogenicity of C. glabrata were retrieved and reviewed from four credible databases, mainly Google Scholar, ScienceDirect, PubMed, and Scopus. The articles highlighted many virulence factors associated with pathogenicity in C. glabrata, including adherence to a susceptible host surface, evading host defences, and producing hydrolytic enzymes (e.g., phospholipases, proteases, and haemolysins). The factors facilitate infection initiation. Other virulent factors include iron regulation and genetic mutations. Accordingly, biofilm production, tolerance to high-stress environments, and development of resistance to the antifungal drug, notably to fluconazole and other azole derivatives, were reported. The review provided evident pathogenic mechanisms and antifungal resistance associated with C. glabrata in ensuring its sustenance and survival.

scholarly journals Autotransporter secretion exploits the bacterial actin-homologue

2018 ◽  
Author(s):  
Mahmoud M. Ashawesh ◽  
Robert Markus ◽  
Christopher N. Penfold ◽  
Kim R. Hardie
Keyword(s):  
Bacterial Infection ◽  
Virulence Factors ◽  
Pathogenic Bacteria ◽  
Super Resolution ◽  
Resistance Mechanisms ◽  
Dynamic Interaction ◽  
Bacterial Toxins ◽  
Gram Negative ◽  
Bacterial Cytoskeleton ◽  
Development Of Resistance

AbstractBacterial infection of humans, animals and plants relies heavily on secreted proteases that degrade host defences or activate bacterial toxins. The largest family of proteins secreted by Gram-negative pathogenic bacteria, the Autotransporters (ATs), includes key proteolytic virulence factors. There remains uncertainty about the mechanistic steps of the pathway ATs share to exit bacteria, and how it is energetically driven. This study set out to shed light on the AT secretion pathway with the ultimate aim of uncovering novel antimicrobial targets that would be unlikely to trigger the development of resistance mechanisms in bacteria. To do this, two AT virulence factors with distinct proteolytic functions, EspC (secreted from EnteropathogenicEscherichia coli) and AaaA (tethered to the extracellular surface ofPseudomonas aeruginosa) were chosen. EspC and AaaA were fluorescently labelled using two separate methods to establish the localization patterns of ATs as they are secreted from a bacterial cell. Super resolution microscopy revealed that localization of ATs occurs via a helical route along the bacterial cytoskeleton. In addition to requiring the conserved C-terminal β-barrel translocator domain of the AT, we present the first evidence that secretion is dependent on a dynamic interaction with a structure reliant upon the actin homologue MreB and the Sec translocon. These findings provide a step forward in the mechanistic understanding of the secretion of this widely distributed family of proteins that have pivotal roles in bacterial pathogenesis and conserved structural properties that could serve as novel broad-range antimicrobial targets.SignificanceSecreted bacterial proteases facilitate the infection of human, animal and plant hosts by degrading host defences or activating bacterial toxins. The autotransporter family is the largest family of proteins secreted from Gram-negative bacteria, and includes proteolytic virulence factors crucial to bacterial infection. Precisely how autotransporters migrate from the inside to the outside of the cell, and how this movement is energetically driven is a mystery. We demonstrate a spiral pathway of autotransporter secretion, presenting evidence that it involves a dynamic interaction with the actin homologue MreB that comprises the bacterial cytoskeleton. Our findings open the way to unravelling the mechanism of autotransporter secretion and offer the possibility to identify novel antimicrobial targets unlikely to trigger the development of antimicrobial resistance.

scholarly journals Antifungal Resistance Regarding Malassezia pachydermatis: Where Are We Now?

2020 ◽  
Vol 6 (2) ◽  
pp. 93
Author(s):  
Andrea Peano ◽  
Elizabeth Johnson ◽  
Elisa Chiavassa ◽  
Paolo Tizzani ◽  
Jacques Guillot ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Antifungal Agents ◽  
Standard Procedure ◽  
Resistance Mechanisms ◽  
Antifungal Resistance ◽  
Antifungal Drugs ◽  
Malassezia Pachydermatis ◽  
Development Of Resistance ◽  
Ear Canals

Malassezia pachydermatis is a yeast inhabiting the skin and ear canals in healthy dogs. In the presence of various predisposing conditions it can cause otitis and dermatitis, which are treated with multiple antifungal agents, mainly azole derivatives. This manuscript aims to review the available evidence regarding the occurrence of resistance phenomena in this organism. Various findings support the capacity of M. pachydermatis for developing resistance. These include some reports of treatment failure in dogs, the reduced antifungal activity found against yeast isolates sampled from dogs with exposure to antifungal drugs and strains exposed to antifungal agents in vitro, and the description of resistance mechanisms. At the same time, the data reviewed may suggest that the development of resistance is a rare eventuality in canine practice. For example, only three publications describe confirmed cases of treatment failure due to antifungal resistance, and most claims of resistance made by past studies are based on interpretive breakpoints that lack sound support from the clinical perspective. However, it is possible that resistant cases are underreported in literature, perhaps due to the difficulty of obtaining a laboratory confirmation given that a standard procedure for susceptibility testing of M. pachydermatis is still unavailable. These considerations highlight the need for maintaining surveillance for the possible emergence of clinically relevant resistance, hopefully through a shared strategy put in place by the scientific community.

Urinary Tract Infections in Patients with Type 1 and Type 2 Diabetes: Etiology, Resistance to Antibacterial Chemicals and Virulence Features

2017 ◽  
Vol 68 (3) ◽  
pp. 566-569 ◽  
Author(s):  
Mihaela Magdalena Mitache ◽  
Carmen Curutiu ◽  
Elena Rusu ◽  
Ramona Bahna ◽  
Mara Ditu ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Virulence Factors ◽  
Urinary Tract Infections ◽  
Disk Diffusion ◽  
Diffusion Method ◽  
Diabetic Patients ◽  
Disk Diffusion Test ◽  
Tract Infections ◽  
Susceptibility Profiles ◽  
Diabetes Patients

One of the most frequent chronic complications occurred in diabetes patients are the urinary tract infections (UTIs). This study aimed to investigate the incidence of UTIs in a cohort of 93 (47 males: 46 females) diabetic patients, the prevalence of different microbial species involved and their virulence and antibiotic resistance profiles. The identification of the uropathogenic strains in the positive urine samples was performed using conventional methods and API tests. After identification, the antibiotic susceptibility profiles were established by the standardized disk diffusion method and double disk diffusion test was performed for the confirmation of ESBL and inducible AmpC b �lactamase phenotypes. The isolated strains were tested for the production of different cell associated and soluble virulence factors, i.e.: bacterial adherence to cellular substrata (HeLa cells), hemolysins (hemolysis spot, CAMP-like), amylase, caseinase, aesculin hydrolysis, DNA-ase, lipase and lecithinase. In the analyzed group, the total prevalence of UTIs was of 46%, a higher incidence being observed in the female patients (64%). Similar to other studies, the etiology of UTI in the investigated diabetes patients was dominated by E. coli, followed by Klebsiella sp. strains. The isolated strains preserved good susceptibility rates to quinolones and aminoglycosides and revealed important virulence features, related to their capacity to colonize the cellular substratum and to produce soluble virulence factors involved in persistence, colonization and progression of the infectious process. The high percentage of beta-lactam resistant strains (including carbapenem-resistant ones) requires careful surveillance of the dynamics of susceptibility profiles for limiting the emergence of these strains in community.

scholarly journals A Narrative Review on Sarcopenia in Type 2 Diabetes Mellitus: Prevalence and Associated Factors

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 183
Author(s):  
Anna Izzo ◽  
Elena Massimino ◽  
Gabriele Riccardi ◽  
Giuseppe Della Pepa
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Elderly Population ◽  
The Elderly ◽  
Narrative Review ◽  
Macrovascular Complications ◽  
Diabetic Patients ◽  
Age Related

Type 2 diabetes mellitus (T2DM) represents a major health burden for the elderly population, affecting approximately 25% of people over the age of 65 years. This percentage is expected to increase dramatically in the next decades in relation to the increased longevity of the population observed in recent years. Beyond microvascular and macrovascular complications, sarcopenia has been described as a new diabetes complication in the elderly population. Increasing attention has been paid by researchers and clinicians to this age-related condition—characterized by loss of skeletal muscle mass together with the loss of muscle power and function—in individuals with T2DM; this is due to the heavy impact that sarcopenia may have on physical and psychosocial health of diabetic patients, thus affecting their quality of life. The aim of this narrative review is to provide an update on: (1) the risk of sarcopenia in individuals with T2DM, and (2) its association with relevant features of patients with T2DM such as age, gender, body mass index, disease duration, glycemic control, presence of microvascular or macrovascular complications, nutritional status, and glucose-lowering drugs. From a clinical point of view, it is necessary to improve the ability of physicians and dietitians to recognize early sarcopenia and its risk factors in patients with T2DM in order to make appropriate therapeutic approaches able to prevent and treat this condition.

scholarly journals 651. Comparative Analysis Between Bacterial And Fungal Malignant Otitis Externa

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S383-S384
Author(s):  
Fatma Hammami ◽  
Makram Koubaa ◽  
Amal Chakroun ◽  
Fatma Smaoui ◽  
Khaoula Rekik ◽  
...  
Keyword(s):  
Otitis Externa ◽  
Clinical Presentation ◽  
The Elderly ◽  
Causative Organism ◽  
Diabetic Patients ◽  
Duration Of Treatment ◽  
Evolutionary Features ◽  
Significant Difference ◽  
Malignant Otitis Externa ◽  
History Of

Abstract Background Malignant otitis externa is a fatal infection of the external ear and temporal bone. Pseudomonas aeruginosa is the most common causative organism, while fungi are a rare cause of malignant otitis externa. We aimed to compare the clinical, therapeutic and evolutionary features between bacterial and fungal malignant otitis externa. Methods We conducted a retrospective study including all patients hospitalized for malignant otitis externa in the infectious diseases department between 2000 and 2018. Results Overall, we encountered 82 cases of malignant otitis externa, among which there were 54 cases (65.9%) of bacterial malignant otitis externa (BMO) and 28 cases (34.1%) of fungal malignant otitis externa (FMO). The males were predominant among BMO cases (57.4% vs 50%; p=0.5). Patients with FMO were significantly older (70±9 years vs 61±10 years; p< 0.001) and had medical history of diabetes mellitus more frequently (96.4% vs 77.8%; p=0.03). The use of topical corticosteroids was significantly more reported among FMO cases (28.6% vs 5.6%; p=0.006). Otalgia (96.4% vs 81.5%), otorrhea (75% vs 66.7%) and cephalalgia (46.4% vs 42.6%) were the revealing symptoms among FMO and BMO, respectively, with no significant difference. Tenderness to palpation of the mastoid bone (64.3% vs 38.9%; p=0.02) and stenosis of the external auditory canal (92.9% vs 72.2%; p=0.02) were significantly more frequent among FMO cases. Complications were significantly more frequent among FMO cases (42.9% vs 9.3%; p< 0.001). Treatment duration was significantly longer among FMO cases (70[40-90] days vs 45[34-75] days; p=0.03). Conclusion Our study showed that FMO affected more frequently the elderly and diabetic patients, when compared with BMO. Regardless of the causative agent, the clinical presentation was similar. However, the outcome was poor among FMO cases with the occurrence of complications, requiring a longer duration of treatment. Disclosures All Authors: No reported disclosures

scholarly journals Silver (I) N-Heterocyclic Carbene Complexes: A Winning and Broad Spectrum of Antimicrobial Properties

2021 ◽  
Vol 22 (5) ◽  
pp. 2497
Author(s):  
Filippo Prencipe ◽  
Anna Zanfardino ◽  
Michela Di Napoli ◽  
Filomena Rossi ◽  
Stefano D’Errico ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Antimicrobial Properties ◽  
Resistance Mechanisms ◽  
Heterocyclic Carbenes ◽  
Significant Activity ◽  
Bacterial Strains ◽  
Development Of Resistance ◽  
Starting Point ◽  
Catalytic Chemistry

The evolution of antibacterial resistance has arisen as the main downside in fighting bacterial infections pushing researchers to develop novel, more potent and multimodal alternative drugs.Silver and its complexes have long been used as antimicrobial agents in medicine due to the lack of silver resistance and the effectiveness at low concentration as well as to their low toxicities compared to the most commonly used antibiotics. N-Heterocyclic Carbenes (NHCs) have been extensively employed to coordinate transition metals mainly for catalytic chemistry. However, more recently, NHC ligands have been applied as carrier molecules for metals in anticancer applications. In the present study we selected from literature two NHC-carbene based on acridinescaffoldand detailed nonclassicalpyrazole derived mono NHC-Ag neutral and bis NHC-Ag cationic complexes. Their inhibitor effect on bacterial strains Gram-negative and positivewas evaluated. Imidazolium NHC silver complex containing the acridine chromophore showed effectiveness at extremely low MIC values. Although pyrazole NHC silver complexes are less active than the acridine NHC-silver, they represent the first example of this class of compounds with antimicrobial properties. Moreover all complexesare not toxic and they show not significant activity againstmammalian cells (Hek lines) after 4 and 24 h. Based on our experimental evidence, we are confident that this promising class of complexes could represent a valuable starting point for developing candidates for the treatment of bacterial infections, delivering great effectiveness and avoiding the development of resistance mechanisms.

scholarly journals Virulence of Clinical Candida Isolates

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 466
Author(s):  
Martyna Mroczyńska ◽  
Anna Brillowska-Dąbrowska
Keyword(s):  
Virulence Factors ◽  
Biofilm Formation ◽  
Galleria Mellonella ◽  
Hydrolytic Enzymes ◽  
Morphological Transition ◽  
Candida Spp

The factors enabling Candida spp. infections are secretion of hydrolytic enzymes, adherence to surfaces, biofilm formation or morphological transition, and fitness attributes. The aim of this study was to investigate the correlation between known extracellular virulence factors and survival of Galleria mellonella larvae infected with clinical Candida. The 25 isolates were tested and the activity of proteinases among 24/24, phospholipases among 7/22, esterases among 14/23, hemolysins among 18/24, and biofilm formation ability among 18/25 isolates was confirmed. Pathogenicity investigation using G. mellonella larvae as host model demonstrated that C. albicans isolates and C. glabrata isolate were the most virulent and C. krusei isolates were avirulent. C. parapsilosis virulence was identified as varied, C. inconspicua were moderately virulent, and one C. palmioleophila isolate was of low virulence and the remaining isolates of this species were moderately virulent. According to our study, virulence of Candida isolates is related to the expression of proteases, hemolysins, and esterases.

scholarly journals Development of Resistance in Wild-Type and Hypermutable Pseudomonas aeruginosa Strains Exposed to Clinical Pharmacokinetic Profiles of Meropenem and Ceftazidime Simulated In Vitro

2007 ◽  
Vol 51 (10) ◽  
pp. 3642-3649 ◽  
Author(s):  
Beate Henrichfreise ◽  
Irith Wiegand ◽  
Ingeborg Luhmer-Becker ◽  
Bernd Wiedemann
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Parent Strain ◽  
Resistance Mechanisms ◽  
In Vitro Models ◽  
Wild Type ◽  
Resistance Development ◽  
Development Of Resistance ◽  
Pharmacokinetic Profiles ◽  
Mutant Prevention Concentration

ABSTRACT In this study we investigated the interplay of antibiotic pharmacokinetic profiles and the development of mutation-mediated resistance in wild-type and hypermutable Pseudomonas aeruginosa strains. We used in vitro models simulating profiles of the commonly used therapeutic drugs meropenem and ceftazidime, two agents with high levels of antipseudomonal activity said to have different potentials for stimulating resistance development. During ceftazidime treatment of the wild-type strain (PAO1), fully resistant mutants overproducing AmpC were selected rapidly and they completely replaced wild-type cells in the population. During treatment with meropenem, mutants of PAO1 were not selected as rapidly and showed only intermediate resistance due to the loss of OprD. These mutants also replaced the parent strain in the population. During the treatment of the mutator P. aeruginosa strain with meropenem, the slowly selected mutants did not accumulate several resistance mechanisms but only lost OprD and did not completely replace the parent strain in the population. Our results indicate that the commonly used dosing regimens for meropenem and ceftazidime cannot avoid the selection of mutants of wild-type and hypermutable P. aeruginosa strains. For the treatment outcome, including the prevention of resistance development, it would be beneficial for the antibiotic concentration to remain above the mutant prevention concentration for a longer period of time than it does in present regimens.

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