I am Noura M. Seleem lecturer of Microbiology and Immunology at Zagazig University, Egypt. I am interested in inhibiting bacterial virulence, interfering with quorum sensing and combating nosocomial infections like Acinetobacter and Pseudomonas.
Protecting food from bacterial contamination is crucial for ensuring its safety and avoiding food... more Protecting food from bacterial contamination is crucial for ensuring its safety and avoiding foodborne illness. Serratia marcescens is one of the food bacterial contaminants that can form biofilms and pigments that spoil the food product and could cause infections and illness to the consumer. Food preservation is essential to diminish such bacterial contaminants or at least reduce their pathogenesis; however, it should not affect food odor, taste, and consistency and must be safe. Sodium citrate is a well-known safe food additive and the current study aims to evaluate its anti-virulence and anti-biofilm activity at low concentrations against S. marcescens. The anti-virulence and antibiofilm activities of sodium citrate were evaluated phenotypically and genotypically. The results showed the significant effect of sodium citrate on decreasing the biofilm formation and other virulence factors, such as motility and the production of prodigiosin, protease, and hemolysins. This could be ow...
The current failure of antimicrobials in treating life-threatening diseases, the high rate of mul... more The current failure of antimicrobials in treating life-threatening diseases, the high rate of multidrug resistant pathogens and the slow progress in the development of new antibiotics directed scientists to develop antivirulence drugs that targets quorum sensing (QS). In many microbes, QS acts as a communication system which inhibits pathogenicity of microbes and stop the infection. Analgesics can be beneficial in controlling virulence traits of microbes and hence they may augment the efficacy of antimicrobials. In this study, two analgesics were screened for the inhibition of QS in Chromobacterium violaceum CV026 and their effects on virulence production in Pseudomonas aeruginosa PAO1 strain and clinical isolates of Acinetobacter baumannii were evaluated. The traits investigated were biofilm formation, pyocyanin and rhamnolipid production, twitching swarming or surface associated motilities, production of protease, phospholipase and gelatinase enzymes and sensitivity to oxidative stress. Relative expression of abaI gene was calculated by performing qRT-PCR. Docking analysis of paracetamol as QSI (quorum sensing inhibitor) of AbaI and AbaR proteins was performed. Paracetamol inhibited QS in CV026, but indomethacin devoids anti-QS activity. Paracetamol inhibited virulence factors of PAO1. It strongly inhibited biofilm formation, and swarming by 66.4% and 57.1%, respectively. While, it moderately to slightly inhibited rhamnolipid, pyocyanin, gelatinase, resistance to oxidative stress, protease and twitching motility by 33.3%, 33.1% 17.5%, 9.1%, 8.7% and 7.7%, respectively. For A. baumannii, paracetamol strongly inhibited biofilm by 39.7-93% and phospholipase enzyme by 8.7-100%, reduced twitching and surface motility by 6.7-82.5% and 7.7-29.4%, respectively, And slightly reduced sensitivity to oxidative stress by 3.3-36.4%. Paracetamol at sub-MIC suppressed the expression of abaI gene by 32% in A. baumannii. Docking studies suggested that paracetamol can bind to AbaR and AbaI proteins and bind more to AbaR, hence it may act by inhibiting AHL signal reception. As a conclusion, paracetamol, beside its analgesic activity, has anti-QS activity and could be used in the eradication of P. aeruginosa and A. baumannii infections in combination with antibiotics.
Sofosbuvir and Daclatasvir are among the direct‐acting antiviral (DAA) medications prescribed for... more Sofosbuvir and Daclatasvir are among the direct‐acting antiviral (DAA) medications prescribed for the treatment of chronic hepatitis C (CHC) virus infection as combination therapy with other antiviral medications. DAA‐based therapy achieves high cure rates, reaching up to 97% depending on the genotype of the causative hepatitis C virus (HCV). While DAAs have been approved as an efficient and well‐tolerated therapy for CHC, emerging concerns about adverse cardiac side effects, higher risk of recurrence and occurrence of hepatocellular carcinoma (HCC) and doubts of genotoxicity have been reported. In our study, we investigated in detail physiological off‐targets of DAAs and dissected the effects of these drugs on cellular organelles using budding yeast, a unicellular eukaryotic organism. DAAs were found to disturb the architecture of the endoplasmic reticulum (ER) and the mitochondria, while showing no apparent genotoxicity or DNA damaging effect. Our study provides evidence that DAAs are not associated with genotoxicity and highlights the necessity for adjunctive antioxidant therapy to mitigate the adverse effects of DAAs on ER and mitochondria.
The emergence of multidrug-resistant (MDR) strains is a major health problem worldwide. There is ... more The emergence of multidrug-resistant (MDR) strains is a major health problem worldwide. There is an urgent need for novel strategies to combat bacterial infections caused by MDR strains like Pseudomonas aeruginosa and Acinetobacter baumannii. Quorum sensing (QS) is a critical communication system in bacterial community controlling survival and virulence. The awareness of the importance of QS in bacterial infections has stimulated research to identify QS inhibitors (QSIs) to defeat microbes. In this study, four FDA-approved drugs (besides azithromycin as positive QSI) were tested for potential QS inhibition against clinical A. baumannii isolates and P. aeruginosa (PAO1) standard strain. The inhibitory effect of these drugs on virulence factors of both microbes has been investigated. The studied virulence factors include biofilm formation, twitching and swarming motilities, proteolytic enzyme production, and resistance to oxidative stress. The four tested drugs (erythromycin, levamisole, chloroquine, and propranolol) inhibited QS in Chromobacterium violaceum by 84, 72, 55.1, and 37.3%, respectively. They also significantly inhibited virulence factors in both PAO1 and A. baumannii at sub-inhibitory concentrations. These findings were confirmed by qRT-PCR and mice mortality test, where tested drugs highly repressed the expression of abaI gene and showed significantly improved mice survival rates. In addition, molecular docking studies against AbaI and AbaR proteins of QS system in A. baumannii revealed the potential inhibition of QS by tested drugs. Beside their known activities, the tested drugs could be given new life as QSIs to combat A. baumannii nosocomial infections (alone or in combination with antimicrobials).
Bacteria communicate with each other by producing chemical signals (acyl homoserine lactones, AHL... more Bacteria communicate with each other by producing chemical signals (acyl homoserine lactones, AHLs) through the quorum sensing (QS) signaling circuits, which control the expression of virulence genes. Also QS plays a significant role in biofilm formation, therefore it is important to develop new strategies to inhibit QS and get rid of biofilm. Acinetobacter baumannii is a major nosocomial pathogen that has a high resistance to antimicrobials and dessication. In addition, it has a strong ability to form biofilm in chronic infections. In the present study, quantification of biofilm and screening of MDR A. baumannii for QS signal molecules (AHLs) were performed. Out of the 52 MDR Acinetobacter baumannii isolates, 42 isolates were found to be strong biofilm formers. Out of the 42 strong biofilm forming isolates, 20 isolates produced long chain AHL signals and none of them produced short chain AHL signals. The results revealed that 81% of the isolates formed strong biofilm and 48% of the strong biofilm forming isolated have QS activity, which indicates that QS has a potential role in the control of A. baumannii biofilm formation.
Acinetobacter baumannii is a significant nosocomial pathogen with multiple drug resistance and em... more Acinetobacter baumannii is a significant nosocomial pathogen with multiple drug resistance and emerging resistance to carbapenems (the last resort drugs), so the treatment of Acinetobacter baumannii hospital-acquired infections is very complex. In this study the detection of the carbapenemase enzymes responsible for carbapenem resistance in imipenem resistant A. baumannii clinical isolates isolated from intensive care units (ICUs) was performed. This detection was carried out on a genotypic and phenotypic basis. Out of 32 isolates of Acinetobacter baumannii from ICUs of Zagazig University hospitals, Sharkia, Egypt, 24 imipenem resistant isolates were used to detect carbapenemases producers. The modified Hodge test, the AmpC Disk test, and Combined disk test using EDTA with CAZ and IPM were performed for the screening of carbapenemase, Amp C enzyme and metallo-β-lactamase production respectively. Polymerase chain reaction (PCR) assay were performed for the detection of genes encoding for OXA-23-like, OXA-24-like, OXA-51-like and OXA-58-like carbapenemase. All isolates showed 84.37% resistance to cefepime and cefuroxime, 81.25% resistance to cefotaxime, 78.1% resistance to ceftriaxone,75% resistance to ceftazidime, meropenem and imipenem,71.9% resistance to pipracillin, 65.6% resistance to amikacin trimethprim/sulfamethoxazole and ofloxacin, 68.75% resistance to ciprofloxacin, 59.37% resistance to and gentamicin, 46.88% resistance to levofloxacin. All isolates were sensitive to colistin. All of the 24 isolates (100%) showed positive results in the modified Hodge test and positive results in the Amp C disk test and Combined disk test. They all (100%) possessed the encoding gene for an intrinsic OXA-51-like carbapenemase and an acquired OXA-23-like carbapenemase in the PCR assay. The results revealed that all of the 24 Imipenem resistant Acinetobacter baumannii [IRAB] isolates acquired resistance to carbapenem by producing metallo-β-lactamase and OXA-23 carbapenemase.
Protecting food from bacterial contamination is crucial for ensuring its safety and avoiding food... more Protecting food from bacterial contamination is crucial for ensuring its safety and avoiding foodborne illness. Serratia marcescens is one of the food bacterial contaminants that can form biofilms and pigments that spoil the food product and could cause infections and illness to the consumer. Food preservation is essential to diminish such bacterial contaminants or at least reduce their pathogenesis; however, it should not affect food odor, taste, and consistency and must be safe. Sodium citrate is a well-known safe food additive and the current study aims to evaluate its anti-virulence and anti-biofilm activity at low concentrations against S. marcescens. The anti-virulence and antibiofilm activities of sodium citrate were evaluated phenotypically and genotypically. The results showed the significant effect of sodium citrate on decreasing the biofilm formation and other virulence factors, such as motility and the production of prodigiosin, protease, and hemolysins. This could be ow...
The current failure of antimicrobials in treating life-threatening diseases, the high rate of mul... more The current failure of antimicrobials in treating life-threatening diseases, the high rate of multidrug resistant pathogens and the slow progress in the development of new antibiotics directed scientists to develop antivirulence drugs that targets quorum sensing (QS). In many microbes, QS acts as a communication system which inhibits pathogenicity of microbes and stop the infection. Analgesics can be beneficial in controlling virulence traits of microbes and hence they may augment the efficacy of antimicrobials. In this study, two analgesics were screened for the inhibition of QS in Chromobacterium violaceum CV026 and their effects on virulence production in Pseudomonas aeruginosa PAO1 strain and clinical isolates of Acinetobacter baumannii were evaluated. The traits investigated were biofilm formation, pyocyanin and rhamnolipid production, twitching swarming or surface associated motilities, production of protease, phospholipase and gelatinase enzymes and sensitivity to oxidative stress. Relative expression of abaI gene was calculated by performing qRT-PCR. Docking analysis of paracetamol as QSI (quorum sensing inhibitor) of AbaI and AbaR proteins was performed. Paracetamol inhibited QS in CV026, but indomethacin devoids anti-QS activity. Paracetamol inhibited virulence factors of PAO1. It strongly inhibited biofilm formation, and swarming by 66.4% and 57.1%, respectively. While, it moderately to slightly inhibited rhamnolipid, pyocyanin, gelatinase, resistance to oxidative stress, protease and twitching motility by 33.3%, 33.1% 17.5%, 9.1%, 8.7% and 7.7%, respectively. For A. baumannii, paracetamol strongly inhibited biofilm by 39.7-93% and phospholipase enzyme by 8.7-100%, reduced twitching and surface motility by 6.7-82.5% and 7.7-29.4%, respectively, And slightly reduced sensitivity to oxidative stress by 3.3-36.4%. Paracetamol at sub-MIC suppressed the expression of abaI gene by 32% in A. baumannii. Docking studies suggested that paracetamol can bind to AbaR and AbaI proteins and bind more to AbaR, hence it may act by inhibiting AHL signal reception. As a conclusion, paracetamol, beside its analgesic activity, has anti-QS activity and could be used in the eradication of P. aeruginosa and A. baumannii infections in combination with antibiotics.
Sofosbuvir and Daclatasvir are among the direct‐acting antiviral (DAA) medications prescribed for... more Sofosbuvir and Daclatasvir are among the direct‐acting antiviral (DAA) medications prescribed for the treatment of chronic hepatitis C (CHC) virus infection as combination therapy with other antiviral medications. DAA‐based therapy achieves high cure rates, reaching up to 97% depending on the genotype of the causative hepatitis C virus (HCV). While DAAs have been approved as an efficient and well‐tolerated therapy for CHC, emerging concerns about adverse cardiac side effects, higher risk of recurrence and occurrence of hepatocellular carcinoma (HCC) and doubts of genotoxicity have been reported. In our study, we investigated in detail physiological off‐targets of DAAs and dissected the effects of these drugs on cellular organelles using budding yeast, a unicellular eukaryotic organism. DAAs were found to disturb the architecture of the endoplasmic reticulum (ER) and the mitochondria, while showing no apparent genotoxicity or DNA damaging effect. Our study provides evidence that DAAs are not associated with genotoxicity and highlights the necessity for adjunctive antioxidant therapy to mitigate the adverse effects of DAAs on ER and mitochondria.
The emergence of multidrug-resistant (MDR) strains is a major health problem worldwide. There is ... more The emergence of multidrug-resistant (MDR) strains is a major health problem worldwide. There is an urgent need for novel strategies to combat bacterial infections caused by MDR strains like Pseudomonas aeruginosa and Acinetobacter baumannii. Quorum sensing (QS) is a critical communication system in bacterial community controlling survival and virulence. The awareness of the importance of QS in bacterial infections has stimulated research to identify QS inhibitors (QSIs) to defeat microbes. In this study, four FDA-approved drugs (besides azithromycin as positive QSI) were tested for potential QS inhibition against clinical A. baumannii isolates and P. aeruginosa (PAO1) standard strain. The inhibitory effect of these drugs on virulence factors of both microbes has been investigated. The studied virulence factors include biofilm formation, twitching and swarming motilities, proteolytic enzyme production, and resistance to oxidative stress. The four tested drugs (erythromycin, levamisole, chloroquine, and propranolol) inhibited QS in Chromobacterium violaceum by 84, 72, 55.1, and 37.3%, respectively. They also significantly inhibited virulence factors in both PAO1 and A. baumannii at sub-inhibitory concentrations. These findings were confirmed by qRT-PCR and mice mortality test, where tested drugs highly repressed the expression of abaI gene and showed significantly improved mice survival rates. In addition, molecular docking studies against AbaI and AbaR proteins of QS system in A. baumannii revealed the potential inhibition of QS by tested drugs. Beside their known activities, the tested drugs could be given new life as QSIs to combat A. baumannii nosocomial infections (alone or in combination with antimicrobials).
Bacteria communicate with each other by producing chemical signals (acyl homoserine lactones, AHL... more Bacteria communicate with each other by producing chemical signals (acyl homoserine lactones, AHLs) through the quorum sensing (QS) signaling circuits, which control the expression of virulence genes. Also QS plays a significant role in biofilm formation, therefore it is important to develop new strategies to inhibit QS and get rid of biofilm. Acinetobacter baumannii is a major nosocomial pathogen that has a high resistance to antimicrobials and dessication. In addition, it has a strong ability to form biofilm in chronic infections. In the present study, quantification of biofilm and screening of MDR A. baumannii for QS signal molecules (AHLs) were performed. Out of the 52 MDR Acinetobacter baumannii isolates, 42 isolates were found to be strong biofilm formers. Out of the 42 strong biofilm forming isolates, 20 isolates produced long chain AHL signals and none of them produced short chain AHL signals. The results revealed that 81% of the isolates formed strong biofilm and 48% of the strong biofilm forming isolated have QS activity, which indicates that QS has a potential role in the control of A. baumannii biofilm formation.
Acinetobacter baumannii is a significant nosocomial pathogen with multiple drug resistance and em... more Acinetobacter baumannii is a significant nosocomial pathogen with multiple drug resistance and emerging resistance to carbapenems (the last resort drugs), so the treatment of Acinetobacter baumannii hospital-acquired infections is very complex. In this study the detection of the carbapenemase enzymes responsible for carbapenem resistance in imipenem resistant A. baumannii clinical isolates isolated from intensive care units (ICUs) was performed. This detection was carried out on a genotypic and phenotypic basis. Out of 32 isolates of Acinetobacter baumannii from ICUs of Zagazig University hospitals, Sharkia, Egypt, 24 imipenem resistant isolates were used to detect carbapenemases producers. The modified Hodge test, the AmpC Disk test, and Combined disk test using EDTA with CAZ and IPM were performed for the screening of carbapenemase, Amp C enzyme and metallo-β-lactamase production respectively. Polymerase chain reaction (PCR) assay were performed for the detection of genes encoding for OXA-23-like, OXA-24-like, OXA-51-like and OXA-58-like carbapenemase. All isolates showed 84.37% resistance to cefepime and cefuroxime, 81.25% resistance to cefotaxime, 78.1% resistance to ceftriaxone,75% resistance to ceftazidime, meropenem and imipenem,71.9% resistance to pipracillin, 65.6% resistance to amikacin trimethprim/sulfamethoxazole and ofloxacin, 68.75% resistance to ciprofloxacin, 59.37% resistance to and gentamicin, 46.88% resistance to levofloxacin. All isolates were sensitive to colistin. All of the 24 isolates (100%) showed positive results in the modified Hodge test and positive results in the Amp C disk test and Combined disk test. They all (100%) possessed the encoding gene for an intrinsic OXA-51-like carbapenemase and an acquired OXA-23-like carbapenemase in the PCR assay. The results revealed that all of the 24 Imipenem resistant Acinetobacter baumannii [IRAB] isolates acquired resistance to carbapenem by producing metallo-β-lactamase and OXA-23 carbapenemase.
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