Background: The rapid emergence of antimicrobial resistance among Gram-positive organisms, especially staphylococci, has become a serious clinical challenge. Efflux machinery and biofilm formation are considered two of the main causes of antimicrobial resistance and therapy failure. Aim: Our study aims to evaluate the antibiofilm and efflux pump inhibitory activity of the antifungal ketoconazole against multidrug-resistant (MDR) Staphylococcus aureus. Methods: Ketoconazole was tested for its effect on the following: minimum inhibitory con- centrations (MICs) of ciprofloxacin, norfloxacin, levofloxacin, and ethidium bromide (EtBr) by the broth microdilution method, the efflux of EtBr by NorA-positive MDR S. aureus, and the relative expression of NorA, NorB, and NorC efflux pump genes. Docking studies of ketocona- zole were performed using 1PW4 (glycerol-3-phosphate transporter from Escherichia coli which was the representative structure from the major facilitator superfamily). Results: Ketoconazole significantly decreased the MICs of levofloxacin, ciprofloxacin, norfloxacin, and EtBr (a substrate for efflux pump) by 8 to 1024-fold (P0.01) and decreased the efflux of EtBr. Furthermore, a time-kill assay revealed that combinations of levofloxacin with ketoconazole or carbonyl cyanide m-chlorophenylhydrazone showed no growth for the tested strains after 24 h in comparison to the effect of levofloxacin alone. Docking studies and the ability of ketoconazole to diminish the relative expression of NorA gene in compar- ison to control (untreated strains) confirmed its action as an efflux pump inhibitor. Conclusion: The findings showed that the antifungal ketoconazole has no antibacterial activity but can potentiate the activity of the fluroquinolones against MDR S. aureus via inhibiting efflux pump and biofilm formation in vitro. Keywords: ketoconazole, efflux pump, biofilm, Nor genes

Background and Aim: Nanosized inorganic antibacterial materials have received increasing attention in recent years. The present study aimed to determine the anti- microbial activity of silver (Ag) and zinc oxide (ZnO) nanoparticles alone and in combination with antibiotics against reference strains of pathogenic microorganisms as Staphylococcus aureus (Staph. aureus), Salmonella enterica subsp. Bukuru, Escherichia coli (E.coli) and Candida albicans ( C. albicans). Methods: The antimicrobial effect of metal-nanoparticles (AgNPs and ZnONPS) and in combination with antibiotics was studied using the normal disc-diffusion method. Results: Both AgNPs and ZnONPs had increased antibacterial activity with an increase in their concentration against Gram-positive bacterium (Staph. aureus), Gram-negative bacteria (E. coli and Salmonella spp) and no effect on C. albicans. The synergistic effect of antibiotics (azithromycin, cefotaxime, cefuroxime, fosfomycin and chloramphenicol) against E. coli was significantly increased in the presence of AgNPs compared to antibiotic only. However, all antibiotics had a synergistic effect in the presence of AgNps against Salmonella spp. On the other hand, the antibacterial action of AgNPs with oxacillin and neomycin antibiotics against Staph. aureus was significantly decreased in comparison with antibiotics only. The synergistic effect of antibiotics (azithromycin, oxacillin, cefotaxime, cefuroxime, fosfomycin and oxytetracycline) against E. coli was significantly increased in presence of ZnONPs compared to antibiotic only and also the synergistic effect of antibiotics (azithro- mycin, cefotaxime, cefuroxime, fosfomycin, chloramphenicol and oxytetracycline) against Staph. aureus was significantly increased in the presence of ZnONPs compared to antibiotics only. On the other hand, most antibiotics had an antagonistic effect in presence of ZnONps against Salmonella spp.

Disturbances in autophagy are known to be implicated in autoimmune disorders. Many studies have connected polymorphisms in autophagy-related gene 5 (ATG-5) to systemic lupus erythematosus (SLE). Our aim was the determination of the expres￾sion level of ATG-5, Beclin-1 and microtubule-associated protein-light chain 3 (LC- 3) in Egyptian SLE patients to investigate the impact of disturbances in autophagy genes on the incidence and progression of the disease. Also, we investigated the incidence of single nucleotide polymorphism (SNP) rs573775 in ATG-5 gene among Egyptian SLE patients. Our results showed that the mean levels of Beclin-1, LC-3 and interleukin (IL)-10 transcripts were significantly higher in SLE patients compared to healthy controls. The previous transcripts were positively correlated with SLE Disease Activity Index (SLEDAI). Beclin-1 and LC-3 transcripts were negatively cor￾related to complement component 3 (C3) levels. Only LC-3 transcripts were nega￾tively correlated to complement component 4 (C4). The rs573775 SNP of ATG-5 with the variant allele was significantly associated with disease susceptibility, conferring a higher risk of SLE development. This variant allele was more prevalent in patients below 30 years, patients with anemia and in patients with anti-double-stranded DNA (dsDNA), confirming the essential role of ATG-5 polymorphism in the susceptibility of Egyptian patients to SLE.

Disturbances in autophagy are known to be implicated in autoimmune disorders. Many studies have connected polymorphisms in autophagy-related gene 5 (ATG-5) to systemic lupus erythematosus (SLE). Our aim was the determination of the expres￾sion level of ATG-5, Beclin-1 and microtubule-associated protein-light chain 3 (LC- 3) in Egyptian SLE patients to investigate the impact of disturbances in autophagy genes on the incidence and progression of the disease. Also, we investigated the incidence of single nucleotide polymorphism (SNP) rs573775 in ATG-5 gene among Egyptian SLE patients. Our results showed that the mean levels of Beclin-1, LC-3 and interleukin (IL)-10 transcripts were significantly higher in SLE patients compared to healthy controls. The previous transcripts were positively correlated with SLE Disease Activity Index (SLEDAI). Beclin-1 and LC-3 transcripts were negatively cor￾related to complement component 3 (C3) levels. Only LC-3 transcripts were nega￾tively correlated to complement component 4 (C4). The rs573775 SNP of ATG-5 with the variant allele was significantly associated with disease susceptibility, conferring a higher risk of SLE development. This variant allele was more prevalent in patients below 30 years, patients with anemia and in patients with anti-double-stranded DNA (dsDNA), confirming the essential role of ATG-5 polymorphism in the susceptibility of Egyptian patients to SLE.

Disturbances in autophagy are known to be implicated in autoimmune disorders. Many studies have connected polymorphisms in autophagy-related gene 5 (ATG-5) to systemic lupus erythematosus (SLE). Our aim was the determination of the expres￾sion level of ATG-5, Beclin-1 and microtubule-associated protein-light chain 3 (LC- 3) in Egyptian SLE patients to investigate the impact of disturbances in autophagy genes on the incidence and progression of the disease. Also, we investigated the incidence of single nucleotide polymorphism (SNP) rs573775 in ATG-5 gene among Egyptian SLE patients. Our results showed that the mean levels of Beclin-1, LC-3 and interleukin (IL)-10 transcripts were significantly higher in SLE patients compared to healthy controls. The previous transcripts were positively correlated with SLE Disease Activity Index (SLEDAI). Beclin-1 and LC-3 transcripts were negatively cor￾related to complement component 3 (C3) levels. Only LC-3 transcripts were nega￾tively correlated to complement component 4 (C4). The rs573775 SNP of ATG-5 with the variant allele was significantly associated with disease susceptibility, conferring a higher risk of SLE development. This variant allele was more prevalent in patients below 30 years, patients with anemia and in patients with anti-double-stranded DNA (dsDNA), confirming the essential role of ATG-5 polymorphism in the susceptibility of Egyptian patients to SLE.

Disturbances in autophagy are known to be implicated in autoimmune disorders. Many studies have connected polymorphisms in autophagy-related gene 5 (ATG-5) to systemic lupus erythematosus (SLE). Our aim was the determination of the expres￾sion level of ATG-5, Beclin-1 and microtubule-associated protein-light chain 3 (LC- 3) in Egyptian SLE patients to investigate the impact of disturbances in autophagy genes on the incidence and progression of the disease. Also, we investigated the incidence of single nucleotide polymorphism (SNP) rs573775 in ATG-5 gene among Egyptian SLE patients. Our results showed that the mean levels of Beclin-1, LC-3 and interleukin (IL)-10 transcripts were significantly higher in SLE patients compared to healthy controls. The previous transcripts were positively correlated with SLE Disease Activity Index (SLEDAI). Beclin-1 and LC-3 transcripts were negatively cor￾related to complement component 3 (C3) levels. Only LC-3 transcripts were nega￾tively correlated to complement component 4 (C4). The rs573775 SNP of ATG-5 with the variant allele was significantly associated with disease susceptibility, conferring a higher risk of SLE development. This variant allele was more prevalent in patients below 30 years, patients with anemia and in patients with anti-double-stranded DNA (dsDNA), confirming the essential role of ATG-5 polymorphism in the susceptibility of Egyptian patients to SLE.

Disturbances in autophagy are known to be implicated in autoimmune disorders. Many studies have connected polymorphisms in autophagy-related gene 5 (ATG-5) to systemic lupus erythematosus (SLE). Our aim was the determination of the expres￾sion level of ATG-5, Beclin-1 and microtubule-associated protein-light chain 3 (LC- 3) in Egyptian SLE patients to investigate the impact of disturbances in autophagy genes on the incidence and progression of the disease. Also, we investigated the incidence of single nucleotide polymorphism (SNP) rs573775 in ATG-5 gene among Egyptian SLE patients. Our results showed that the mean levels of Beclin-1, LC-3 and interleukin (IL)-10 transcripts were significantly higher in SLE patients compared to healthy controls. The previous transcripts were positively correlated with SLE Disease Activity Index (SLEDAI). Beclin-1 and LC-3 transcripts were negatively cor￾related to complement component 3 (C3) levels. Only LC-3 transcripts were nega￾tively correlated to complement component 4 (C4). The rs573775 SNP of ATG-5 with the variant allele was significantly associated with disease susceptibility, conferring a higher risk of SLE development. This variant allele was more prevalent in patients below 30 years, patients with anemia and in patients with anti-double-stranded DNA (dsDNA), confirming the essential role of ATG-5 polymorphism in the susceptibility of Egyptian patients to SLE.

Simple Summary: Sarcoptic mange is an important zoonotic parasite aecting camel production. Mange zoonosis in camels is complicated by scarcity of available data. One of the main strategies for disease control is early detection of the parasite combined with prevention/control of the major risk factors associated with the infection. The present study focused on the prevalence of sarcoptic mange in camels from Egypt together with a histopathological examination of the parasite and association of the major risk factors, to describe the epidemiological pattern of the disease. Our data demonstrate that 47.6% of the camels harbored sarcoptic mange infections. In addition, the animals exhibited obvious clinical signs of mange and numerous histopathological findings that are consistent with sarcoptic mange. The camel’s age, gender and sampling season were found to be the most significant risk factors associated with the disease. Taken together, our epidemiological and histopathological data are consistent with sarcoptic mange being widespread among camels in the studied area. Our study suggests further research is needed for management of this zoonotic disease in Egypt. Abstract: Mange has been considered one of the most common parasitic infestations among camels. It adversely impacts animal productivity and poses a risk to human health. Given the scarcity of available data about mange in camels, the current study focused on the prevalence of camel mange and its associated risk factors in Aswan Governorate, Egypt. Towards this end, a general visual inspection was conducted on camels (N = 210) in dierent markets and slaughterhouses in Aswan Governorate. Animals 2020, 10, 1485; doi:10.3390/ani10091485 www.mdpi.com/journal/animals Animals 2020, 10, 1485 2 of 11 Skin scrapings from suspect infected camels were also examined microscopically. Importantly, these findings were further checked and confirmed by histopathology on samples from suspected cases collected post-slaughter in abattoirs. The possible risk-associated factors, which include the camel’s age, sex and sampling season, were recorded and statistically analyzed. Interestingly, the data showed that a total of 100 camels (47.6%) were found exclusively infested by sarcoptic mange. Furthermore, the predominant histopathological changes included burrowing tunnel of mites in the skin, hyperkeratosis and acanthosisconsis of the epidermis, while the dermis showed hemorrhage, mononuclear inflammatory cell infiltration around the blood vessels and perifolliculitis. These major histopathological findings are consistent with sarcoptic mange. Furthermore, the statistical analysis of the possible associated risk factors, camel’s age (p = 0.006), gender (p = 0.032) and sampling season (p = 0.004), were all found to be significantly aected and related to the disease. In this regard, camels 2 years old were found at higher risk of infection (odds ratio (OR) = 2.75; 95% confidence interval (CI), 1.345 to 5.604) versus younger animals (OR = 0.36; 95 CI, 0.1784 to 0.743). Females had higher odds of exposure (OR = 2.02; 95% CI, 1.096 to 3.708) compared to males (OR = 0.50; 95% CI, 0.269 to 0.912). Moreover, the exposure to infection was reported higher in winter (OR = 2.30; 95% CI, 1.297 to 4.098) than in summer (OR = 0.43; 95% CI, 0.244 to 0.771). Collectively, our data provide novel epidemiological and histopathological support for sarcoptic mange being widespread among camels in the studied area. Sarcoptic mange is extremely contagious and zoonotic. Therefore, our baseline investigation indicates an urgent need for additional multicenter-studies to investigate the occurrence of this disease in camels and humans combined with the appropriate control measures of camel importation for combating this disease.

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