scholarly journals Monoclonal IgM antibodies raised against Candida albicans Hyr1 provide cross-kingdom protection against Gram negative bacteria

2019 ◽  
Author(s):  
Eman G. Youssef ◽  
Sondus Alkhazraji ◽  
Teclegiorgis Ghebremariam ◽  
Lina Zhang ◽  
Shakti Singh ◽  
...  

AbstractRecent years have seen an unprecedented rise in the incidence of multidrug resistant (MDR) Gram negative bacteria (GNB) such as Acinetobacter and Klebsiella species. In view of the shortage of novel drugs in the pipeline, alternative strategies to prevent and treat infections by GNB are urgently needed. Previously, we have reported that the C. albicans hyphal-regulated protein Hyr1 shares striking 3D structural homology with cell surface proteins of A. baumannii; and active or passive vaccination with rHyr1p-N or anti-Hyr1p polyclonal antibody, respectively; protect mice from Acinetobacter infections. Here, we show that monoclonal antibodies (mAb) generated against Hyr1p, bind to the surface of Acinetobacter as well as K. pneumoniae. The anti-Hyr1 mAb also block damage to primary endothelial cells by the bacteria, and protect mice from lethal pulmonary infections mediated by A. baumannii and K. pneumoniae. Our current studies emphasize the potential of harnessing Hyr1p mAb as a cross-kingdom immunotherapeutic strategy against MDR GNB.

BIO-PROTOCOL ◽  
2017 ◽  
Vol 7 (9) ◽  
Author(s):  
Carlos Eduardo da Cunha ◽  
Jane Newcombe ◽  
Odir Dellagostin ◽  
Johnjoe McFadden

2021 ◽  
Author(s):  
Xukai Jiang ◽  
Nitin A. Patil ◽  
Mohammad A. K. Azad ◽  
Hasini Wickremasinghe ◽  
Heidi Yu ◽  
...  

Multidrug-resistant Gram-negative bacteria have been an urgent threat to global public health. Novel antibiotics are desperately needed to combat these 'superbugs'.


Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 340
Author(s):  
Raquel Bandeira da Silva ◽  
Mauro José Salles

Gram-negative bacteria (GNB), including multidrug-resistant (MDR) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). This retrospective observational study identified independent risk factors (RFs) associated with MDR-GNB PJI and their influence on treatment outcomes. We assessed MDR bacteria causing hip and knee PJIs diagnosed at a Brazilian tertiary hospital from January 2014 to July 2018. RFs associated with MDR-GNB PJI were estimated by bivariate and multivariate analyses using prevalence ratios (PRs) with significance at p < 0.05. Kaplan–Meier analysis was performed to evaluate treatment outcomes. Overall, 98 PJI patients were analysed, including 56 with MDR-GNB and 42 with other bacteria. Independent RFs associated with MDR-GNB PJI were revision arthroplasty (p = 0.002), postoperative hematoma (p < 0.001), previous orthopaedic infection (p = 0.002) and early infection (p = 0.001). Extensively drug-resistant GNB (p = 0.044) and comorbidities (p = 0.044) were independently associated with MDR-GNB PJI treatment failure. In sum, MDR-GNB PJI was independently associated with previous orthopaedic surgery, postoperative local complications and pre-existing infections and was possibly related to selective pressure on bacterial skin colonisation by antibiotics prescribed for early PJI. Infections due to MDR-GNB and comorbidities were associated with higher treatment failure rates.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shira Mandel ◽  
Janna Michaeli ◽  
Noa Nur ◽  
Isabelle Erbetti ◽  
Jonathan Zazoun ◽  
...  

AbstractNew antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S457-S457
Author(s):  
Henry Pablo Lopes Campos e Reis ◽  
Ana Beatriz Ferreira Rodrigues ◽  
Julio César Castro Silva ◽  
Lia Pinheiro de Lima ◽  
Talita Lima Quinaher ◽  
...  

Abstract Background Enterobacteria and multidrug-resistant non-fermenting Gram-negative bacilli present a challenge in the management of invasive infections, leading to mortality rates due to their limited therapeutic arsenal. The objective of this work was to analyze risk factors that may be associated with these infections, for a better situational mapping and assertive decision-making in a university hospital in Brazil. Methods The study was conducted between January and September 2019, with 167 patients in contact isolation at a university hospital in Brazil. Potential outcome-related variables for wide-resistance Gram-negative bacteria (BGN) infections were evaluated. Risk factors were identified from univariate statistical analysis using Fisher’s test. Results 51 (30.5%) out of 167 patients in contact isolation evolved with wide-resistance BGN infection. Risk factors in univariate analysis were age, hospital unit and previous use of invasive devices. Patients aged up to 59 years were more likely to progress to infection than those aged over 60 years (p 0.0274, OR 2.2, 95% CI 1.1-4.5). Those admitted to the oncohematology (p &lt; 0.001, OR 32.5, Cl 9.1-116.3) and intensive care unit (p &lt; 0.001, OR 28.0, Cl 3.5-225.9) units were more likely to develop this type of infection. The least likely were those admitted to a kidney transplant unit (p 0.0034, OR 15.33, Cl 1.8-131.0). Prior use of mechanical ventilation (p 0.0058, OR 12.2, Cl 2.0-76.1) and delayed bladder catheter (p 0.0266, OR 5.0, Cl 1.2-20.1) in patients with respiratory and urinary tract infection, respectively, were also reported as risk factors related to these infections. The gender of the patients was not significant for the study. Conclusion This study determined that variables such as age, hospitalization unit, use of mechanical ventilation and delayed bladder catheter could be considered important risk factors in triggering the infectious process by wide-resistant gram-negative bacteria. Thus, the analysis of these factors becomes a great foundation to prevent the development of multiresistant pathogens through prevention strategies, prophylaxis management and more targeted empirical therapies. Disclosures All Authors: No reported disclosures


2014 ◽  
Vol 35 (9) ◽  
pp. 1203-1204
Author(s):  
Enrico Schalk ◽  
Jacqueline Färber ◽  
Thomas Fischer

Gaia Scientia ◽  
2021 ◽  
Vol 15 (2) ◽  
Author(s):  
Raul Vítor Ferreira de Oliveira ◽  
Margareth Borges Coutinho Gallo ◽  
Oscarina Viana de Sousa ◽  
Álef Vasconcelos Ribeiro ◽  
Tatiana Salata Lima ◽  
...  

Brazil is among the world’s largest consumers of pesticides, with glyphosate (GLY) being the most commercialized herbicide in the country. Studies showed microorganisms suffer selective pressure when exposed to pesticides, developing tolerance to pesticides and resistance to antibiotics (ABs), in a phenomenon known as “cross-resistance”. The present work aimed to evaluate the occurrence of glyphosate-tolerance and AB-resistance in bacteria isolated from different agricultural management systems in Ceará State, Brazil. Gram-negative bacteria isolated from agroforestry (S1), conventional farming (S2) and uncultivated (S3) soils were cultured in the presence of 1.6% acid glyphosate. Overall, 58 strains were isolated. Soils S1 and S2 presented several multidrug resistant (MDR) strains, the majority resistant to ampicilin. Although there was a small percentage of strains resistant to ertapenem (33%, soil S1), the fact they were found is concerning, as Carbapenem antibiotics are used to treat clinical cases of MDR bacteria, which are not common outside hospital settings. Stenotrophomonas maltophilia (soil S2), resistant to six of the eight ABs tested, was identified by MALDI-TOF mass spectrometry, and was found as one of the most common opportunistic bacteria in ICUs of Ceará hospitals.


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