Overview of Proteus mirabilis pathogenicity and virulence. Insights into the role of metals.

Proteus mirabilis is a Gram-negative bacterium with exclusive molecular and biological features. It is a versatile pathogen acclaimed for its distinct urease production, swarming behavior, and rapid multicellular activity. Clinically, P. mirabilis is a frequent pathogen of the human urinary system where it causes urinary tract infections (UTIs) and catheter-associated urinary tract infections (CAUTIs). This review explores the epidemiology, risk factors, clinical manifestations, and treatment of P. mirabilis infections, emphasizing its association with UTIs. The bacterium's genome analysis revealed the presence of resistance genes against commonly used antibiotics, an antibiotic-resistant phenotype that poses a serious clinical challenge. Particularly, the emergence of extended-spectrum ß-lactamases (ESBLs) and carbapenemases resistant P. mirabilis strains. On a molecular level, P. mirabilis possesses a wide array of virulence factors including the production of fimbriae, urease, hemolysins, metallophores, and biofilm formation. This review thoroughly tackles a substantial gap in understanding the role of metallophores in shaping the virulence factors of P. mirabilis virulence. Siderophores, iron metal chelating and transporting metallophores, particularly contribute to the complex pathogenic strategies, displaying a potential target for therapeutic intervention.

The Emergence of SARS-CoV-2 Variant(s) and Its Impact on the Prevalence of COVID-19 Cases in the Nabatieh Region, Lebanon.

Background: An outbreak of an unknown respiratory illness caused by a novel coronavirus, SARS-CoV-2, emerged in the city of Wuhan in Hubei Province, China, in December 2019 and was referred to as coronavirus disease-2019 (COVID-19). Soon after, it was declared as a global pandemic by the World Health Organization (WHO) in March 2020. SARS-CoV-2 mainly infects the respiratory tract with different outcomes ranging from asymptomatic infection to severe critical illness leading to death. Different SARS-CoV-2 variants are emerging of which three have raised concerns worldwide due to their high transmissibility among populations. Objective: To study the prevalence of COVID-19 in the region of Nabatieh-South Lebanon during the past year and assess the presence of SARS-CoV-2 variants and their effect on the spread of infection during times of lockdown. Methods: In our study, 37,474 nasopharyngeal swab samples were collected and analyzed for the detection of SARS-CoV-2 virus in suspected patients attending a tertiary health care center in South Lebanon during the period between 16 March 2020 and 21 February 2021. Results: The results demonstrated a variation in the prevalence rates ranging from less than 1% during full lockdown of the country to 8.4% upon easing lockdown restrictions and reaching 27.5% after the holidays and 2021 New Year celebrations. Interestingly, a new variant(s) appeared starting January 2021 with a significant positive association between the prevalence of positive tests and the percentage of the variant(s). Conclusions: Our results indicate that the lockdown implemented by the Lebanese officials was an effective intervention to contain COVID-19 spread. Our study also showed that lifting lockdown measures during the holidays, which allowed indoor crowded gatherings to occur, caused a surge in COVID-19 cases and rise in the mortality rates nationwide. More importantly, we confirmed the presence of a highly transmissible SARS-CoV-2 variant(s) circulating in the Lebanese community from at least January 2021 onwards.

Prevalence, Laboratory Findings and Clinical Characteristics of Campylobacteriosis Agents among Hospitalized Children with Acute Gastroenteritis in Lebanon.

PURPOSE: Campylobacter species are currently the most common cause of bacterial gastroenteritis. In Lebanon, Campylobacter infection occurrence is underdiagnosed owing to the lack of specific culture and rapid test kits, particularly among children. This study aimed to evaluate the prevalence, laboratory findings, and clinical characteristics of Campylobacter infection in hospitalized children with acute gastroenteritis in South Lebanon. METHODS: We conducted a 6-month retrospective cohort study between January and June 2018, including 291 children aged between 1 month and 12 years, who were admitted to a tertiary healthcare center in South Lebanon. The medical files of the patients were reviewed to retrieve the required clinical information, including clinical and laboratory data. RESULTS: The prevalence of campylobacteriosis agents in pediatric patients with acute gastroenteritis is 12.02%. Patients infected with Campylobacter had more severe acute gastroenteritis than Campylobacter-negative patients and often presented with high-grade fever, diarrhea episodes more than six times per day, diarrhea lasting for more than five days, and dehydration. Indeed, children with high-grade fever (≥38.5°C) were five times more likely to test positive for Campylobacter than those with low-grade fever. In addition, the results showed a higher Vesikari score for the majority of Campylobacter-positive patients with severe acute gastroenteritis compared to a moderate profile for Campylobacter-negative patients. CONCLUSION: The present study findings highlight that Campylobacter infection is frequent among children with acute gastroenteritis. Therefore, the detection of Campylobacter should be carried out for the diagnosis of human gastroenteritis in Lebanon, along with the detection of routine enteropathogens.

Antimicrobial Susceptibilities and Laboratory Profiles of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis Isolates as Agents of Urinary Tract Infection in Lebanon: Paving the Way for Better Diagnostics.

Background: Urinary tract infections (UTIs) are major healthcare problems that are usually treated empirically. However, antimicrobial resistance has been increasing across many settings. This study aims to elucidate the antibiotic resistance profiles of three common uropathogens, Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Proteus mirabilis (P. mirabilis) and compare between extended spectrum beta-lactamase (ESBL) and non-ESBL strains among Lebanese patients. Methods: This retrospective study was conducted at multiple tertiary healthcare centers in South Lebanon, between January and September 2017, including 551 patients of all age groups. Demographic, clinical, and laboratory data of patients were collected and analyzed statistically. Results: The prevalence of UTI in Lebanon was highest in adults between 19 and 64 years (44%). E. coli was the predominant uropathogenic organism (67.1%) followed by K. pneumoniae (10%) and P. mirabilis (3.7%). ESBL represented 32.9% of the UTI agents. The three common uropathogens studied were found to be most susceptible to imipenem (100%) and meropenem (100%). Interestingly, 115 (25.1%) out of the 458 E. coli isolates were resistant to more than eight antibiotics while 107 (23.4%) were susceptible to all antibiotics studied. Conclusions: Our study underlined the importance of adequate antimicrobial prescription for UTIs in Lebanon to avoid multidrug resistance.

Spectrum of MEFV Variants and Genotypes among Clinically Diagnosed FMF Patients from Southern Lebanon.

Background: Familial Mediterranean Fever (FMF) is an autosomal recessive auto-inflammatory disease characterized by pathogenic variants in the MEFV gene, with allele frequencies greatly varying between countries, populations and ethnic groups. Materials and methods: In order to analyze the spectrum of MEFV variants and genotypes among clinically diagnosed FMF patients from South Lebanon, data were collected from 332 participants and 23 MEFV variants were screened using a Real-Time PCR Kit. Results: The mean age at symptom onset was 17.31 ± 13.82 years. The most prevalent symptoms were abdominal pain, fever and myalgia. MEFV molecular analysis showed that 111 patients (63.79%) were heterozygous, 16 (9.20%) were homozygous, and 47 (27.01%) carried two variants or more. E148Q was the most encountered variant among heterozygous subjects. E148Q/M694V was the most frequent in the compound heterozygous/complex genotype group, while M694I was the most common among homozygous patients. Regarding allele frequencies, M694V was the most common variant (20.7%), followed by E148Q (17.1%), V726A (15.7%) and M694I (13.2%). Conclusion: The high percentage of heterozygous patients clinically diagnosed as FMF highlights the pseudo-dominant transmission of the disease in Lebanon and emphasizes the importance of molecular testing for a more accurate diagnosis and better management and treatment of FMF.

Prevalence, risk factors, and clinical characteristics of rotavirus and adenovirus among Lebanese hospitalized children with acute gastroenteritis.

BACKGROUND: Acute gastroenteritis is a very common infectious disease facing all age groups worldwide, especially the pediatric population. Viruses, bacteria, and parasites are all possible causes of infectious gastroenteritis; however, viruses have become more frequently identified with the advances in the ability to diagnose viral infections, particularly rotavirus and adenovirus. We aimed in our study to compare between the prevalence, risk factors, and clinical characteristics of rotavirus and adenovirus among children with viral gastroenteritis in Lebanon. MATERIALS AND METHODS: A 12-months retrospective study was performed between January 1st and December 31st, 2018 including 308 children aged 1 month to 12 years, who were admitted to three tertiary healthcare centers in South Lebanon. Medical data were retrieved from patients' files, including clinical and laboratory information. RESULTS: Rotavirus was found in stool of 204 patients (66.23 %), followed by adenovirus in 78 cases (25.32 %), and mixed group (rotavirus and adenovirus) in 26 cases (8.44%). The highest prevalence of rotavirus in our present study was seen among children between 12 and 23 months old, whereas patients infected with adenovirus were mainly aged between 24-35 months or 4-11 months. Majority of patients in the adenovirus and mixed groups had high-grade fever compared to the rotavirus group. Laboratory findings presented significantly higher average of white blood cells (WBCs), absolute neutrophil count (ANC), and C-reactive protein (CRP) in the mixed group compared to the two other groups. Monthly distribution of rotavirus and adenovirus infection revealed a biennial pattern of rotavirus incidence during January and July-August while frequency of adenovirus infection was highest during July-August. CONCLUSION: Due to the high prevalence of viral diarrhea among the pediatric age group in our region, particularly rotavirus and adenovirus, along with the associated non-specific signs and symptoms, we highly recommend that medical laboratories be equipped for virus detection. Also, vaccination against rotavirus should be considered as a prevention strategy.

Emergence of Vulvovaginal Candidiasis among Lebanese Pregnant Women: Prevalence, Risk Factors, and Species Distribution.

Objective: Candida species colonize the vagina in at least 20% of women, with rates rising to 30% during pregnancy. This study aimed at determining the prevalence and risk factors of vulvovaginal candidiasis (VVC) in pregnant women at 35-37 weeks of gestation. It also aims at finding possible correlations between VVC and vaginal colonization by other agents, such as Group B Streptococcus (GBS) and bacterial vaginosis. Methodology: Over a one-year period, high vaginal swabs were collected from pregnant women during their regular antenatal checkup in different polyclinics in Beirut and South Lebanon. Swabs were examined microscopically, cultured on Sabouraud Dextrose Agar, and Candida isolates were identified using Chromatic Candida medium and Germ Tube Test. Results: VVC was detected in 44.8% of samples, with C. glabrata (44.4%) and C. albicans (43.4%) being the most isolated species. Approximately, half of pregnant women (57.7%) were coinfected with Candida and bacterial vaginosis, while 26% of them carried simultaneously Candida spp. and GBS. No significant correlation was found between the occurrence of VVC and demographic, clinical, medical, and reproductive health characteristics of pregnant women. In contrast, participants with previous miscarriages and those being hospitalized during the past 12 months were more susceptible to develop vaginal C. krusei infection in comparison to other Candida species (p=0.0316 and p=0.0042, respectively). Conclusion: The prevalence of VVC in pregnant women is an increasing trend in our community. Therefore, routine medical examination and regular screening for candidiasis in the antenatal care program is highly recommended to manage the disease and its complications.

Prevalence, antimicrobial resistance and risk factors for campylobacteriosis in Lebanon.

INTRODUCTION: The rapid increase in Campylobacter strains resistant to antibiotics represents a major problem for public health. In Lebanon, campylobacteriosis is underdiagnosed since bacteria detection in stool samples is not performed routinely. This study aims to evaluate the prevalence, sources and routes of transmission, risk factors and antimicrobial susceptibility patterns of Campylobacter spp. in Lebanon. METHODOLOGY: Stool samples collected from 1000 Lebanese patients with diarrhea, and 150 meat samples taken from supermarkets and slaughterhouses were subjected to Campylobacter detection. Colonies were identified by Gram staining, oxidase and catalase activities. They were then differentiated at the species level by hippurate test and PCR. Susceptibility of Campylobacter spp. to antibiotics was studied by the disc diffusion standard method. RESULTS: Campylobacter spp. were detected in 21.5% of stool samples; the main isolated species being C. jejuni (83.2%) and C. coli (13.9%). The highest Campylobacter infection rates were detected among children (41.8%) and during summer (31.6%). Consumption of contaminated meat and salads, and contact with animals represented the major risk factors for campylobacteriosis, with poultry carcasses and bovine cuts identified as the main bacteria reservoirs. Neither demographic determinants nor season had a major effect on the prevalence of campylobacteriosis. Erythromycin was the most active agent against Campylobacter spp. A multi-resistance rate was observed in 35.9% of isolates. CONCLUSIONS: Campylobacteriosis is a major public health concern in Lebanon. Bacteria detection in stool culture should be performed routinely to allow an early diagnosis and a better monitoring of the disease and its burden.

Macrophage apolipoprotein E and proliferation of MCF-7 breast cancer cells: role of LXR.

BACKGROUND: Apolipoprotein E (APOE), a lipid transport protein that has a key role in the lipoprotein metabolism, is expressed by macrophages under the control of the transcription factor Liver X Receptor (LXR), an oxysterol-activated transcriptional factor involved in cholesterol metabolism. Recent work has shown that LXR agonists may inhibit breast cancer cell proliferation in vitro. We hypothesized that LXR-activated macrophages, and in particular secreted macrophagic APOE, may potentiate the effect of LXR agonists. Our goal was to evaluate the effect of APOE, secreted by THP-1 macrophages under the control of LXR, on MCF-7 cell proliferation, a model of breast cancer. MATERIALS AND METHODS: MCF-7 cells were incubated with supernatants from THP-1 cells previously treated with LXR agonists [T0901317 or 22(R)-hydroxycholestrol], or supernatants from THP-1 cells transfected with siRNA against APOE mRNA. RESULTS: Viability assays and cell death quantification showed that media from LXR-activated macrophages reduced cell proliferation and increased apoptosis of MCF-7 cells. Interestingly, the opposite effects were observed when MCF-7 cells wre treated with media from the siRNA APOE-mediated knock-down model. CONCLUSION: This study highlights the protective role of LXR-activated macrophages against breast cancer growth, and the implication of APOE protein in the anti-proliferative and pro-apoptotic effects observed.

LXR agonists and ABCG1-dependent cholesterol efflux in MCF-7 breast cancer cells: relation to proliferation and apoptosis.

BACKGROUND: Liver X receptor (LXR) plays a key role in reverse cholesterol transport by inducing the expression of the ATP-binding cassette (ABC) transporters, implicated in cholesterol efflux. Recent data showed that LXR agonists inhibit the proliferation of multiple types of human cancer cells. However, whether these effects are related to cholesterol efflux has not yet been elucidated. MATERIALS AND METHODS: Effects of two LXR agonists (TO901317 and 22(R)-hydroxycholesterol [22(R)-HC]) on proliferation, apoptosis and cholesterol efflux were examined in MCF-7 breast cancer cells. RESULTS: Treatment with LXR agonists (TO901317 at 20 µM and 22(R)-HC at 2 µg/ml) inhibited proliferation and induced apoptosis of MCF-7 cells. Furthermore, LXR activation resulted in an increase in gene and protein levels of ABCG1 transporters and in cholesterol efflux to isolated high-density lipoprotein (HDL), without affecting the ABCA1/APOA-I mediated efflux. Under these conditions, a remarkable reduction of intracellular and membrane-associated cholesterol levels was observed. CONCLUSION: LXR activation in MCF-7 cells could deprive cells of cholesterol, required for their growth, by stimulating its efflux, resulting in the inhibition of cell proliferation and in stimulation of apoptosis.