Pathogens and Global Health最新文献

For people living in developed countries life span is growing at a faster pace than ever. One of the main reasons for such success is attributable to the introduction and extensive use in the clinical practice of antibiotics over the course of the last seven decades. In hospital settings, Klebsiella pneumoniae represents a well-known and commonly described opportunistic pathogen, typically characterized by resistance to several antibiotic classes. On the other hand, the broad wedge of population living in Low and/or Middle Income Countries is increasing rapidly, allowing the spread of several commensal bacteria which are transmitted via human contact. Community transmission has been the original milieu of K. pneumoniae isolates characterized by an outstanding virulence (hypervirulent). These two characteristics, also defined as "pathotypes", originally emerged as different pathways in the evolutionary history of K. pneumoniae. For a long time, the Sequence Type (ST), which is defined by the combination of alleles of the 7 housekeeping genes of the Multi-Locus Sequence Typing, has been a reliable marker of the pathotype: multidrug-resistant clones (e.g. ST258, ST147, ST101) in the Western world and hypervirulent clones (e.g. ST23, ST65, ST86) in the Eastern. Currently, the boundaries separating the two pathotypes are fading away due to several factors, and we are witnessing a worrisome convergence in certain high-risk clones. Here we review the evidence available on confluence of multidrug-resistance and hypervirulence in specific K. pneumoniae clones.

Alveolar Echinococcosis (AE) is a zoonotic parasitic disease caused by Echinococcus multilocularis, but its pathogenesis remains unclear. The primary objective of this study is to explore whether Echinococcus multilocularis protoscoleces (PSCs) regulate macrophage polarization and glucose metabolism by PI3K/Akt/mTOR signaling pathway. We found that large numbers of CD68⁺ macrophages gathered in close liver issue from the lesion in AE patients. PSCs preferentially differentiated into M2 macrophages and the expressions of HK1, PFKL, PKM2, PI3K, Akt, p-Akt, mTOR and p-mTOR increased. The above results show that Echinococcus multilocularis protoscoleces enhance glycolysis to promote M2 macrophages through PI3K/Akt/mTOR signaling pathway.

Leishmaniasis is one of the tropical and subtropical diseases which, according to WHO, has the priority of control. The list of anti-leishmanial drugs is limited and requires side effects, high costs, and long-term treatments. Various species, parasite resistance, and simultaneous diseases are among the factors that affect the effectiveness of treatment. Due to these problems and based on satisfactory records of previous studies using antimicrobial peptides (AMPs) against infectious diseases, this study aimed to evaluate the antileishmanial effect of Leishmania-infected macrophage polyclonal antibody (LIMPA) with or without different concentrations (2, 4, 6, 8, 10, 20, 40, 60, and 100 µg/ml) of CM11 and (40, 80, and 100 µg/ml) BufIIIb, two AMPs, in vitro and their therapeutic effects against CL of Balb/c mice. Results showed that LIMPA induced an anti-proliferative effect on Leishmania major growth in macrophages in vitro and intramacrophage-amastigotes in vivo. CM11 with IC50 of 8.73 and 10.10 μg/ml at 48 hours, and BufIIIb with IC50 of 66.83 and 80.26 μg/ml, at 24 hours showed the most significant inhibition of L. major promastigotes and amastigotes. In addition, the CM11 and BufIIIb, with a CC50 of 9.7 μg/ml and 40.34 μg/ml, showed the most significant inhibition effect on the J774.A1 cell line at 48 hours, respectively. In addition, in vivo experiments using LIMPA with a 0.01 mg/kg dosage showed a significant difference (p < 0.001) in the last week of the measurement compared to the control. The results of this study may be a promising prospect for further investigations.

Bloodstream infections (BSI) are associated with high morbidity and mortality. This study aimed to describe the epidemiology of BSI and antimicrobial resistance patterns amongst its common bacterial causes. We conducted a retrospective record review of blood culture results of patients hospitalized with BSI at University Hospital 'L. Vanvitelli' from 2016 to 2021. For each patient records were obtained from the database using microbiological information. Gram-positive bacteria were the most predominant pathogens followed by Gram-negative bacteria. Among all isolates, bacterial pathogens most frequently identified included coagulase-negative Staphylococci (CoNS), Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and enterococci. We noted a general decrease in antimicrobial resistance amongst BSI pathogens in the latter years of the study. High levels of macrolide and aminoglycoside resistance amongst CoNS were reported. Carbapenem resistance amongst E. coli was barely reported, while resistance rates amongst K. pneumoniae declined considerably between 2018 and 2021. The prevalence of methicillin-resistant S. aureus decreased during the study period while that of methicillin-resistant CoNS remained relatively high throughout. The prevalence of extended spectrum ß-lactamase - producing E. coli increased considerably between 2016 and 2018 but showed a slight decrease thereafter. Conversely, there was a general decline in the resistant rates of extended spectrum ß-lactamase - producing K. pneumoniae between 2016 and 2018 with a similar trend being noted for carbapenem resistance in K. pneumoniae. Continuously monitoring the changes in the trends in BSI microbiological profiles, including pathogen profiles and the associated antibiotic resistance patterns, can help diagnostic approaches, treatment strategies and prevention programs.

Bordetella pertussis is the causative agent of a respiratory infection called pertussis (whooping cough) that can be fatal in newborns and infants. The pathogen produces a variety of antigenic compounds which alone or simultaneously can damage various host cells. Despite the availability of pertussis vaccines and high vaccination coverage around the world, a resurgence of the disease has been observed in many countries. Reasons for the increase in pertussis cases may include increased awareness, improved diagnostic techniques, low vaccine efficacy, especially acellular vaccines, and waning immunity. Many efforts have been made to develop more effective strategies to fight against B. pertussis and one of the strategies is the use of outer membrane vesicles (OMVs) in vaccine formulations. OMVs are attracting great interest as vaccine platforms since they can carry immunogenic structures such as toxins and LPS. Many studies have been carried out with OMVs from different B. pertussis strains and they revealed promising results in the animal challenge and human preclinical model. However, the composition of OMVs differs in terms of isolation and purification methods, strains, culture, and stress conditions. Although the vesicles from B. pertussis represent an attractive pertussis vaccine candidate, further studies are needed to advance clinical research for next-generation pertussis vaccines. This review summarizes general information about pertussis, the history of vaccines against the disease, and the immune response to these vaccines, with a focus on OMVs. We discuss progress in developing an OMV-based pertussis vaccine platform and highlight successful applications as well as potential challenges and gaps.

Aberrant activation of the immune system has been attributed with etiology and pathogenesis of coronavirus disease 2019 (COVID-19). Here, the transcript levels of toll-like receptors (TLRs) were measured in the nasopharyngeal epithelial cells obtained from COVID-19 patients to assess the involvement of these molecules in the clinical outcome of COVID-19 patients. Nasopharyngeal swab samples were used to obtain epithelial cells from 120 COVID-19 patients and 100 healthy controls. COVID-19 cases were classified into those having clinical symptoms/needing for hospitalization, having clinical symptoms/not needing for hospitalization, and those without clinical symptoms‌. The mRNA expression levels of TLRs were measured in the nasopharyngeal epithelial cells. Overall, mRNA expression of TLR1, TLR2, TLR4, and TLR6 was significantly higher in COVID-19 cases compared to controls. The mRNA expression of TLRs were all higher significantly in the samples from COVID-19 patients having clinical symptoms and needing hospitalization as well as in those with clinical symptoms/not needing for hospitalization in comparison to controls. TLR expression was significantly higher in those with clinical symptoms/needing for hospitalization and those with clinical symptoms/not needing for hospitalization compared to COVID-19 cases without clinical symptoms. In cases with clinical symptoms/needing for hospitalization and those with clinical symptoms/not needing for hospitalization, there was a correlation between TLR expression and clinicopathological findings. In conclusion, aberrant expression of TLRs in the nasopharyngeal epithelial cells from COVID-19 cases may predict the severity of the diseases and necessity for supportive cares in the hospital.

The suppressor of the cytokine signaling-1 (SOCS1) gene is a short sequence located on chromosome 16 that functions to induce an appropriate immune response and is an essential physiological regulator of interferon (IFN) signaling. In addition to comparing the global DNA and SOCS1 gene promoter methylation status between our patients with coronavirus disease 2019 (COVID-19) and healthy controls, this study demonstrates the effect of the SOCS1 rs33989964 polymorphism on patients with COVID-19. The study group included 139 patients diagnosed with COVID-19 in our hospital's clinics between June and December 2020, and the control group included 78 healthy individuals. After comparing the initial gene polymorphisms of the patients with the healthy control group, three separate clinical subgroups were formed. The gene polymorphism distribution and the methylation status of SOCS1 were examined in these clinical subgroups. Hypomethylation of the SOCS1 gene was observed in the COVID-19 patient group compared to the healthy control group (p = 0.001). Between the patients divided into two separate clinical subgroups, those with severe and mild infections, the Del/Del genotype of the SOCS1 gene was more common in patients with severe infection than in patients with mild infection (p = 0.018). Patients with the CA/CA and CA/Del genotypes were 0.201 times more likely to have a severe infection (95% CI: 0.057-0.716, p = 0.007). Having a non-Del/Del genotype was a protective factor against severe infection. The effect of the SOCS1 rs33989964 polymorphism and methylation status of the SOCS1 gene throughout the COVID-19 pandemic could be significant contributions to the literature.

Mixed parasitic infections could affect the host immunological responses and re-design the pathogenesis of each other. The impact of Toxoplasma gondii (T. gondii) and Trichinella spiralis (T. spiralis) co-infection on the immune response remains unclear. The objective of the present study was to investigate the possible effect of chronic trichinellosis on the immune response of rats infected with T. gondii virulent RH strain. Animals were divided into four groups: group I: non-infected negative control; group II: infected with T. spiralis; group III: infected with T. gondii and group IV: infected with T. spiralis then infected with T. gondii 35 days post T. spiralis infection (co-infected group). The interaction between T. spiralis and T. gondii was evaluated by histopathological examination of liver and brain tissues, immunohistochemical expression of inducible nitric oxide synthase (iNOS), and β-catenin in the brain tissues, and CD4⁺ and CD8⁺ T cells percentages, and tumor necrosis factor (TNF)-alpha expression in the spleen tissues. Along with, splenic interleukin (IL)-4 and IL-10 mRNA expression levels were measured 15 days post-Toxoplasma infection. Our study revealed that prior infection with T. spiralis leads to attenuation of Th1 response against T. gondii, including iNOS, TNF-α, and CD8⁺ T-cell response with improvement of the histopathological changes in the tissues. In conclusion, in the co-infected rats, a balanced immune response has been developed with the end result, improvement of the histopathological changes in the liver and brain.