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Finding alternative strategies to confront bacterial resistance is an urgent need. Biofilm-forming bacteria have become a serious problem in medicine and industry. Bacteria can use biofilm as a mechanism of resistance against antibacterial drugs and avoid the immune system. The aim of this study was to evaluate the antibacterial activity of Thymus syriacus (T. syriacus) essential oil in a solid and liquid medium and to study its antibiofilm formation activity. The T. syriacus essential oil was extracted from the aerial parts of the plants. The minimum inhibitory concentrations (MIC) measurements were used to identify the antibacterial activity of the essential oil against multidrug-resistant strains Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumonia (K. pneumonia), Streptococcus pneumonia (S. pneumonia) isolated clinically from blood infections. The microtiter plate was used in order to quantify biofilm formation by bacteria. The minimum inhibitory concentration (MIC) against the three clinically isolated strains (P. aeruginosa, K. pneumonia, S. pneumonia) were (3.12, 1.56, 3.12 µL/mL) respectively. The formation of biofilm by (P. aeruginosa, K. pneumonia, S. pneumonia) was reduced up to (43%, 50%, 60%) respectively, when the essential oil was applied at MIC concentrations for each strain. The observed antibacterial activity of T. syriacus essential oil was significant against antibacterial-resistant strains and antibiofilm formation activity was identified. The novelty of this study is we confirmed that the essential oil of T. syriacus exhibited not just antibacterial properties but also antibiofilm formation effect. More studies are needed in order to continue studying this oil and evaluate its other medicinal properties and toxicity.

PE_PGRS proteins ofMycobacterium tuberculosis(Mtb) constitute a large family of complex modular proteins whose role is still unclear. Among those, we have previously shown, using the heterologous expression inMycobacterium smegmatis, that PE_PGRS3 containing a unique arginine-rich C-terminal domain, promotes adhesion to host cells. In this study, we investigate the role of PE_PGRS3 and its C-terminal domain directly inMtbusing functional deletion mutants. The results obtained here show that PE_PGRS3 is localized on the mycobacterial cell wall and its arginine-rich C-terminal region protrudes from the mycobacterial membrane and mediatesMtbentry into epithelial cells. Most importantly, this positively charged helical domain specifically binds phosphorylated phosphatidylinositols and cardiolipin, whereas it is unable to bind other phospholipids. Interestingly, administration of cardiolipin and phosphatidylinositol but no other phospholipids was able to turn-off expression ofpe_pgrs3 activated by phosphate starvation conditions. These findings suggest that PE_PGRS3 has the key role to serve as a bridge between mycobacteria and host cells by interacting with specific host phospholipids and extracting them from host cells, for their direct integration or as a source of phosphate, during phases of TB pathogenesis whenMtbis short of phosphate supply.

The rapid emergence of bacterial resistance worldwide is a serious problem, leading to many therapeutic failures and rendering inactive effective antibiotics currently used . This problem has recently been accelerated by conflicts and its related migration. The antibiotic resistance phenomenon is diffused in Syria with a high rate of multi drug resistance cases in gram negative and gram positive organisms during and after the Syrian crisis as a result of misprescribing and overprescribing of antibiotics. The inappropriate use of antibiotic plays an important role in resistance generation. Hence, big efforts are urgently needed by using phenotypic and genetic analysis of bacterial strains against antibiotics to increase characterization and identification of mutant resistant strains and find new strategies to control the spread of antimicrobial resistance infections. This review highlights the antibacterial resistance problem in Syria, showing its negative impact and presenting a sum of efforts that are urgently needed to overcome this problem.

Background: Coronavirus Disease 2019 (COVID-19) has infected millions people worldwide and is continuing to spread rapidly. Patients with COVID-19 may be superinfected with other microorganisms. The prevalence of bacterial superinfection among coronavirus patients is not well understood. Aim: The aim of presenting this case is to highlight the problem of Multi-Drug Resistant (MDR) bacterial infection in COVID-19 patients. Case Presentation: Here we reported a 46 years old patient with the previous history of Escherichia coli urinary tract infection. A few weeks later, the patient was recovered from COVID-19 infection and was treated with antiviral therapy until PCR results become negative. Meanwhile, the patients developed urinary tract infection with MDR Escherichia coli even resistant to imipenem and required a critical treatment. Conclusion: Our finding suggests that greater attention should be paid to coronavirus infection complications and prophylaxis use of antibiotics. In addition, more studies are required to better understand the risk factors which are responsible for the superinfection and emergence of drug-resistant strains during COVID-19 infection.

Tuberculosis (TB) is one of the top 10 causes of death worldwide. This scenario is further complicated by the insurgence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. The identification of appropriate drugs with multi-target affinity profiles is considered to be a widely accepted strategy to overcome the rapid development of resistance. The aim of this study was to discover Food and Drug Administration (FDA)-approved drugs possessing antimycobacterial activity, potentially coupled to an effective multi-target profile. An integrated screening platform was implemented based on computational procedures (high-throughput docking techniques on the target enzymes peptide deformylase and Zmp1) and in vitro phenotypic screening assays using two models to evaluate the activity of the selected drugs against Mycobacterium tuberculosis (Mtb), namely, growth of Mtb H37Rv and of two clinical isolates in axenic media, and infection of peripheral blood mononuclear cells with Mtb. Starting from over 3000 FDA-approved drugs, we selected 29 marketed drugs for submission to biological evaluation. Out of 29 drugs selected, 20 showed antimycobacterial activity. Further characterization suggested that five drugs possessed promising profiles for further studies. Following a repurposing strategy, by combining computational and biological efforts, we identified marketed drugs with relevant antimycobacterial profiles.

International audience; Interferon-γ inducible protein 10 (IP-10), is a potent chemoattractant that promotes migration of monocytes and activated T-cells to inflammation foci. IP-10 is elevated in serum of patients with chronic hepatitis C virus (HCV) and tuberculosis (TB) infections, although it remains to be determined the contribution of IP-10 in restricting Mycobacterium tuberculosis (Mtb) replication. Here, we investigated the impact of IP-10 on mycobacteria replication using the ex vivo model of human whole-blood (WB) assay. In particular, we compared the levels of IP-10 upon infection with different Mtb clinical strains and species of non-tuberculous mycobacteria (NTM) and evaluated how IP-10 may contain bacterial replication. Interestingly, we observed that the inhibition of the host enzyme dipeptidyl peptidase IV (DPP-IV), which inactivates IP-10 through cleavage of two amino acids at the chemokine N-terminus, restricted mycobacterial persistence in WB, supporting the critical role of full length IP-10 in mediating an anti-Mtb response. Addition of recombinant IP-10 expressed in eukaryotic cells enhanced the anti-mycobacterial activity in WB, although no differences were observed when IP-10 containing different proportions of cleaved and non-cleaved forms of the chemokine were added. Moreover, recombinant IP-10 did not exert a direct anti-mycobacterial effect. Our results underscore the clinical relevance of IP-10 in mycobacteria pathogenesis and support the potential outcomes that may derive by targeting the IP-10/CXCR3 pathway as host directed therapies for the treatment of Mtb or NTM infections.

PE_PGRSs of Mycobacterium tuberculosis (Mtb) represent a family of complex and peculiar proteins whose role and function remain elusive. In this study, we investigated PE_PGRS3 and PE_PGRS4, two highly homologous PE_PGRSs encoded by two contiguous genes in the Mtb genome. Using a gene-reporter system in Mycobacterium smegmatis (Ms) and transcriptional analysis in Mtb, we show that PE_PGRS3, but not PE_PGRS4, is specifically expressed under low phosphate concentrations. Interestingly, PE_PGRS3, but not PE_PGRS4, has a unique, arginine-rich C-terminal domain of unknown function. Heterologous expression of PE_PGRS3 in Ms was used to demonstrate cellular localisation of the protein on the mycobacterial surface, where it significantly affects net surface charge. Moreover, expression of full-length PE_PGRS3 enhanced adhesion of Ms to murine macrophages and human epithelial cells and improved bacterial persistence in spleen tissue following infection in mice. Expression of the PE_PGRS3 functional deletion mutant lacking the C-terminal domain in Ms did not enhance adhesion to host cells, showing a phenotype similar to the Ms parental strain. Interestingly, enhanced persistence of Ms expressing PE_PGRS3 did not correlate with increased concentrations of inflammatory cytokines. These results point to a critical role for the ≈ 80 amino acids long, arginine-rich C-terminal domain of PE_PGRS3 in tuberculosis pathogenesis.

Summary Objectives Interferon-γ release assays (IGRA) are designed for diagnosis of tuberculosis (TB) infection, and do not discriminate latent TB infection (LTBI) from active TB. Heparin-binding hemagglutinin antigen (HBHA) emerged as a promising antigen for TB diagnosis when used in IGRA format. Aim of this study was to prospectively evaluate the performance of an HBHA-based IGRA to support TB diagnosis and TB therapy monitoring in children with TB infection or active TB disease. Methods Following clinical, microbiological and radiological assessment, children (0–14 years old) were tested by the QuantiFERON TB-Gold In tube (QFT) assay and an aliquot of whole-blood was stimulated with HBHA and IFNγ evaluated only in QFT-positive subjects. Results Among the 550 children tested, 486 (88.4%) scored negative and 64 (11.6%) positive. None of the QFT-negative had active TB. Among the QFT-positive, 45 were with LTBI and 19 active TB. HBHA-IGRA scored positive in 41/45 children (91.1%) with LTBI and in 6/19 active TB children (31.6%) at diagnosis (p = 0.001); remarkably, 5 of these 6 children with active TB scoring HBHA-positive were asymptomatic. Moreover, following TB-specific therapy, most of the non-HBHA-responding children, gained an HBHA-positive response. Conclusions HBHA-based IGRA is a useful support in TB diagnosis and TB-therapy monitoring in children.

Mycobacterium tuberculosis (Mtb) PE_PGRS33 is a surface-exposed protein that was shown to interact with Toll-like receptor 2 on host macrophages to induce inflammatory signals and promote entry in macrophages. In this study, we investigated PE_PGRS33 as a potential target of a humoral response aimed at hampering key processes in tuberculosis pathogenesis. PE_PGRS33 protein was successfully expressed and purified under native condition in Escherichia coli. The purified protein retained its native functional and biological properties, showing the ability to elicit proinflammatory signals in murine and human macrophages. Interestingly, a polyclonal antiserum raised against native PE_PGRS33 showed no cross-reactions with other mycobacterial proteins. The anti-PE_PGRS33 serum was also able to inhibit Mtb entry into macrophages, but it did not reduce entry of the MtbΔpe_pgrs33 strain. Addition of native recombinant PE_PGRS33 to the MtbΔpe_pgrs33 strain during infection restored the Mtb wild-type entry phenotype in macrophage. Moreover, the anti-PE_PGRS33 serum was able to neutralize the proinflammatory activity of PE_PGRS33 in vitro. Furthermore, mice immunized with native recombinant PE_PGRS33, but not with a DNA vaccine expressing PE_PGRS33, were able to restrict M. smegmatis in vivo. These results highlight the potential use of PE_PGRS33 as a target of a neutralizing humoral response against tuberculosis.

Introduction: Breast cancer is the most common cancer in women and the second most frequent cause of cancer death. Several factors affect response to chemotherapy including nodal status, hormonal status and human epidermal growth factor receptor (Her-2). Aim of Study: The study is aiming at evaluating M30 antigen in serum of patients with locally advanced and metastatic breast cancer and establishing the relation between M30 level and response to chemotherapy. Patients and Methods: The study was performed at Al Bairouni University Hospital and the Faculty of Pharmacy (Damascus-Syria). We have included 60 patients with histologic confirmation of invasive ductal carcinoma of the breast treated with the combination (Docetaxel + Doxorubicin) with M30 levels to be evaluated before treatment and 24 hours after the first and third cycle. Results: M30 level increase in serum 24 hours after the 1st cycle correlated with different kinds of response in 39 patients (P value less than 0.03) with better results in those with Estrogen Receptors (ER) positive patients (P value 0.05). There was no correlation between Her-2 status and response (P value 0.3). Conclusion: M30 level in serum is a useful predictor marker of response to chemotherapy in both locally advanced and metastatic breast cancer.

Lipophilic substituents at benzodioxane C (7) of 3-(benzodioxan-2-ylmethoxy)-2,6-difluorobenzamide improve the antibacterial activity against methicillin-resistant Staphylococcus aureus strains to MIC values in the range of 0.2–2.5 μg/mL, whereas hydrophilic substituents at the same position and modifications at the benzodioxane substructure, excepting for replacement with 2-cromanyl, are deleterious. Some of the lead compounds also exhibit good activity against Mtb . Parallel SARs to those of 3-(2-benzothiazol-2-ylmethoxy)-2,6-difluorobenzamide, well known FtsZ inhibitor, and cells alterations typical of FtsZ inhibition indicate such a protein as the target of these potent antibacterial benzodioxane-benzamides.