Journal of Medical Microbiology and Infectious Diseases
Volume:9 Issue: 3, Summer 2021

HIV-1 gp120 V3 GPGR motif has an essential role in viral invasion, cell fusion, and pathogenesis but presents a significant variability that can implicate neutralizing antibodies and antiretroviral drug resistance. We performed a comprehensive analysis based on 259,288 HIV-1 gp120 amino acid sequences obtained from the Los Alamos National Laboratory (LANL) HIV Sequence Database to infer the global distribution of V3 tetrapeptide motifs. We calculated the frequencies and presented the main variants according to continents and countries. Furthermore, the clinical importance of the most distributed V3 motifs was detailed. Our results showed GPGR and GPGQ as the most commonly found V3 motifs among more than five hundred V3 variant motifs. Motifs with clinical implications are widely distributed around the world. Within the most frequent V3 tetrapeptide motifs set, some variants enable the escape from fusion inhibitor drugs and neutralizing antibodies. Considering that an effective vaccine candidate should elicit broadly neutralizing antibodies while fusion inhibitor drug interaction requires conserved amino acids, the diversity of V3 motifs implicates a great challenge in developing an effective HIV-1 vaccine.

Breast cancer is one of the most important causes of mortality in women. Various factors are involved in the development of cancer, including viruses. Toll-like receptors (TLRs) have an essential role in the innate immune system. The present study investigated the relationship between TLR2 rs5743708 polymorphisms and Torque teno virus (TTV) infection with breast cancer.

Blood samples from 80 women with breast cancer and 80 healthy women were collected, and after DNA extraction, the presence of TTV was investigated by a PCR assay and polymorphism in the TLR2 gene (rs5743708) was explored using the PCR-RFLP method. Also, the physical and chemical properties of TLR2 protein in the two wild and mutant forms were analyzed using the ExPASy database.

Statistical analysis showed that there was no significant relationship between the age and TTV infection; TTV infection and breast cancer; the grade of cancer, and TTV infection; while there were significant relationships between rs5743708 polymorphisms and breast cancer; GG genotype and increased incidence of cancer; TTV infection and rs5743708 polymorphisms. Also, instability index, aliphatic index, grand average of hydropathicity, and molecular weight of TLR2 protein varied in wild and mutant states.

Although there was no significant relationship between TTV infection and breast cancer, the rs5743708 polymorphisms might be involved in TTV infection and breast cancer.

The coronavirus infectious disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a severe global health challenge. The primary target for this virus is the lung. However, SARS-CoV-2 can also attack other organs, including the kidney and liver.  Some COVID-19 case reports demonstrated elevated liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin. Indeed, higher levels of liver enzymes occur in severe cases compared with mild to moderate cases. The relationship between liver injury and COVID-19 might be due to various possible reasons such as reactivation of pre-existing liver disease, viral replication in hepatic cells causing direct cytotoxicity, liver ischemia and hypoxia, cytokine storm, and drug-induced liver injury (DILI). Thus, hepatitis prevention and care services are necessary during the COVID-19 pandemic. For instance, drugs that might reactivate hepatitis B should not be prescribed for treating COVID-19. Generally, the long-term effects of SARS-CoV-2 on human health and various organs are not well understood. This review briefly discusses the relationship between SARS-CoV-2 and liver injury (hepatitis), coinfection of hepatitis and COVID-19, and SARS-CoV-2 infection in autoimmune hepatitis.

Extended-Spectrum β-Lactamases (ESBLs) hydrolyze broad-spectrum cephalosporin, monobactam, and penicillin. This study investigated ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteria in the Gaza strip and explored their susceptibility to various antimicrobials to provide a reference for physicians in managing the hospital infection.

Ninety-six isolates, comprising 69 E. coli and 27 K. pneumoniae were obtained from urine, wound, blood, and ear discharge samples from April-June 2013 in Gaza hospitals. The ESBL-producing isolates were screened using the double-disc diffusion test. Antibiotics susceptibility test was determined by the disc diffusion method on Mueller-Hinton agar, and PCR identified β-lactamases genes.

Our results revealed high rates of ESBL-producing K. pneumoniae (59.3%) and E. coli (39.1%) among isolates. About 65.1% of ESBL-producing isolates were susceptible to imipenem while exhibited 100% resistance to cefotaxime and ampicillin and 74.4% to sulfamethoxazole/trimethoprim. Except for imipenem, higher antibiotic resistance rates were observed among ESBL producers than non-ESBL producers. This study showed that the antimicrobial resistance and ESBLs were higher in K. pneumoniae isolates than E. coli isolates, and most K. pneumoniae isolates harbored simultaneously two or three β-lactamases-encoding genes.

High ESBL-producing rates among K. pneumoniae and E. coli isolates and higher resistance rates to antibiotics among ESBL compared to non-ESBL producing isolates necessitate antimicrobial resistance surveillance and molecular characterization of ESBLs-producing bacteria to achieve a specific treatment.

The rapidly increasing extended-spectrum β-lactamase-producing Pseudomonas aeruginosa is a threat to health. This study aims to detect the rpoD gene and blaOXA-10 and blaOXA-48 genes in imipenem-resistant P. aeruginosa clinical isolates simultaneously by multiplex polymerase chain reaction.

Eighty-five culture plates were collected from patients suspected of Pseudomonas spp infection in Ghaem Hospital and Shahid Shourideh Clinic in Mashhad from January to February 2021. After biochemical identification of P. aeruginosa isolates and the measurement of antibiotic resistance, blaOXA-10, blaOXA-48, and rpoD genes were investigated by multiplex polymerase chain reaction in the imipenem-resistant isolates.

Of 82 P. aeruginosa isolates, 38 (46.34%) were resistant to imipenem, with the highest percentage to carbenicillin (69.5%). All imipenem-resistant P. aeruginosa isolates were confirmed by multiplex PCR using the primers that targeted the rpoD gene. Also, in multiplex PCR, among imipenem-resistant isolates, 10 (26.3%) and 9 (23.6%) had blaOXA-10 and blaOXA-48 genes, respectively.

In addition to molecular identification of P. aeruginosa, the present study simultaneously detected blaOXA-10 and blaOXA-48 genes by multiplex PCR. Application of this multiplex PCR, rapid identification of patients, and timely treatment can reduce the β-lactamase gene prevalence in P. aeruginosa clinical isolates.

In many countries, people use animal dung smoke to treat infections. Ancient physicians Avicenna and Zakaria Razi (Zakariyyā Rāzī) recommended these compounds to treat infections. In rural areas of Iran, people used female donkey dung (Anbarnasara) smoke to treat respiratory tract and burn wound infections. This study evaluates the antibacterial and antifungal properties of Anbarnasara smoke.

The smoke from burning Anbarnasara was collected in a 50%-methanol solution. Following evaporation of methanol at 50ºC, the remaining compound was dissolved in DMSO, and various concentrations (3.1-100 mg/ml) were prepared. The antimicrobial effects of various concentrations (3.1-100 mg/ml) of Anbarnasara smoke solution (ASS) were investigated, using the agar well diffusion method on 15 different microorganisms, including eight standard microorganisms and seven bacteria species from clinical specimens. Also, GC-MS analysis was performed to identify the components in ASS.

Antifungal activity on Candida albicans was observed at 6.2- 100 mg/ml of ASS. Among Gram-positive and Gram-negative bacteria, the most significant inhibition zones belonged to Staphylococcus epidermidis (30.5± 0.70 mm) and Proteus mirabilis (25± 0.00 mm) at 100 mg/ml. GC-MS analysis showed 16 major peak areas, and of identified components, ~50% were phenolic compounds. 

Our results confirmed the ancient physicianschr('39') belief in the antibacterial and antifungal properties of Anbarnasara smoke.

The angiotensin-converting enzyme 2 (ACE2) is the effective primary receptor for SARS-CoV-2. The interaction between ACE2 and the spike protein of the virus is the crucial step for virus entry into the target cells. ACE2 receptor can be blocked by neutralizing antibodies (nAbs) such as CR3022 which targets the virus receptor-binding site. Enhancing the binding affinity between CR3022 and ACE2 would lead to a more efficient blockade of virus entry.

 In this regard, the amino acids with central roles in the binding affinity of CR3022 antibody to spike protein were substituted. The best mutations to increase the affinity of antibodies were also selected based on protein-protein docking and molecular dynamics simulations.

The variants 45 (H:30I/G, H:55D/F, H: 103S/Y, L:59T/F, L:98Y/A), 60(H:31T/D, H:55D/E,  H:103S/Y, L:59T/D, L:98Y/F), 67(H:30I/G, H:55D/F, H:103S/Y, L:56 W/L, L:59T/Y, L:61E/G), 69(H:31T/D,  H:55D/F,   H:103S/Y, L:59T/F, L:98Y/A), and 71(H: 31T/D, H:55D/F, H:103S/Y) with respective binding affinities of -167.3, -167.5, -161.6, -173.0, and -169.8 Kcal/mol had higher binding affinities against the RBD of the SARS-CoV2 spike protein compared to the wild-type Ab.

The engineered antibodies with higher binding affinities against the target protein can improve specificity and sensitivity. Thus, a more successful blockade of the ACE2 is achieved, resulting in a better therapeutic outcome. In silico studies can pave the way for designing these engineered molecules avoiding the economic and ethical challenges.

Heteroresistance is the phenomenon wherein subpopulations of microbes exhibit a range of resistance to an antibiotic and are prevalent in a broad range of microorganisms. Not much data on carbapenem and β-lactams heteroresistance among extra-intestinal pathogenic Escherichia coli (ExPEC) in blood infections is available. This study aimed to investigate the frequency of heteroresistance to β-lactams and carbapenems in ExPEC strains isolated from patientschr('39') blood in Tehran, Iran.

Identification of E. coli isolates was performed using standard biochemical tests, and PFGE was employed to determine the E. coli isolates genotypes. Antibiotic resistance pattern to carbapenems (ertapenem, meropenem, and imipenem), cefotaxime, and cefepime was determined by measuring minimum inhibitory concentration (MIC). The results were used to assess β-lactam and carbapenem heteroresistance in E. coli isolates.

In this study, for the first time, heteroresistance to the antibiotics carbapenem (ertapenem, meropenem, and imipenem), cefotaxime, and cefepime was observed in E. coli isolates from blood samples. Sixteen samples had heteroresistance to antibiotics. Three and two isolates showed heteroresistance to imipenem and ertapenem, respectively. Simultaneous heteroresistance to two carbapenem family antibiotics in three isolates was detected. Also, three isolates showed heteroresistance to cefepime and five to cefotaxime. The imipenem-resistant isolates exhibited a higher level of heteroresistance than those resistant to other carbapenem antibiotics.

 The present study shows that heteroresistance is increasing in Iran. Furthermore, this study demonstrated increasing resistance to the carbapenem family.