Signaling Pathways Targeted by Protozoan Parasites to Inhibit Apoptosis

Apoptosis is a biological process carried out during maturation, remodeling, growth, and developmental processes in tissues, and also represents an important defense mechanism of cells against intracellular microorganisms. In counterpart, diverse intracellular pathogens have developed a wide array of strategies to evade apoptosis and persist inside cells. Apoptotic cell death can be triggered through different intracellular signaling pathways that lead to morphological changes and eventually cell death. Among these pathways, MAPK and PI3K play a central role. The precise control of the signaling pathways that lead to apoptosis is crucial for the maintenance of tissue homeostasis. Paradoxically, these same pathways are utilized during infection by distinct intracellular microorganisms in order to evade recognition by the immune system, inhibit apoptosis, and therefore survive, reproduce, and develop inside cells

Role of Dendritic Cells in Parasitic Infections

Dendritic cells comprise a complex array of cell populations that play a leading role in immune defense. In an immature state, they have the capacity to sense and uptake different antigens. Upon capturing antigens, they become activated, mature, and migrate to lymph nodes where they present antigen-derived peptides to naïve T cells. Due to these excellent surveillance properties, dendritic cells play an important role against parasitic infections. Also, dendritic cells are an important source of IL-12, which is a fundamental proinflammatory cytokine in the control of intracellular parasites. The aim of this chapter is to review the most important characteristics and functions of dendritic cells and their role in the control of infection by parasites

Mechanisms of Resistance to Quinolones

Antimicrobial resistance is a worldwide problem. Various pathogenic bacteria can be resistant to one or several antibiotics, resulting in a serious public health problem. Isolation of pathogenic bacteria resistant to multiple last-generation antibiotics from hospital samples have been reported. In that sense, the isolation of pathogenic strains resistant to members of the quinolone family, from clinical samples, is an increasing phenomenon. Quinolones are a group of synthetic broad-spectrum antimicrobials, whose mechanism of action is the inhibition of DNA gyrase and topoisomerase IV, with the consequent DNA breakdown and cell death due to genotoxic damage. Three mechanisms have been determined by which bacteria can be resistant to quinolones: (1) Chromosomal mutations in coding genes (mutations that alter the objectives of the drug). (2) Mutations associated with the reduction of the intracytoplasmic concentration of quinolones. (3) Plasmid-mediated quinolone resistance genes (plasmids that protect cells from the lethal effects of quinolones). In this chapter, we analyze each of them and provide the most current connections and investigations of these processes

A systematic review of historical and current trends in Chagas disease.

INTRODUCTION: Chagas disease (CD) is caused by Trypanosoma cruzi. When acquired, the disease develops in stages. For diagnosis, laboratory confirmation is required, and an extensive assessment of the patient's health should be performed. Treatment consists of the administration of trypanocidal drugs, which may cause severe adverse effects. The objective of our systematic review was to analyze data contained in the CD published case reports to understand the challenges that patients and clinicians face worldwide. MATERIALS AND METHODS: We performed a systematic review following the PRISMA guidance. PubMed database was explored using the terms 'American trypanosomiasis' or 'Chagas disease'. Results were limited to human case reports written in English or Spanish. A total of 258 reports (322 patients) were included in the analysis. Metadata was obtained from each article. Following this, it was analyzed to obtain descriptive measures. RESULTS: From the sample, 56.2% were males and 43.8% were females. Most cases were from endemic countries (85.4%). The most common clinical manifestations were fever during the acute stage (70.0%), dyspnea during the chronic stage in its cardiac form (53.7%), and constipation during the chronic stage in its digestive form (73.7%). Most patients were diagnosed in the chronic stage (72.0%). Treatment was administered in 56.2% of cases. The mortality rate for the acute stage cases was 24.4%, while for the chronic stage this was 28.4%. DISCUSSION: CD is a parasitic disease endemic to Latin America, with increasing importance due to human and vector migration. In this review, we report reasons for delays in diagnosis and treatment, and trends in medical practices. Community awareness must be increased to improve CD's diagnoses; health professionals should be appropriately trained to detect and treat infected individuals. Furthermore, public health policies are needed to increase the availability of screening and diagnostic tools, trypanocidal drugs, and, eventually, vaccines

Artemisinin and Its Synthetic Derivatives as a Possible Therapy for Cancer

To assess the possibility of using the antimalarial drug artemisinin and its synthetic derivatives as antineoplastic drugs. A Pubmed and Google Scholar (1983–2018) search was performed using the terms artemisinin, cancer, artesunate and Artemisia annua. Case reports and original research articles, review articles, and clinical trials in both humans and animals were evaluated. Both in vitro and in vivo clinical trials and case reports have shown promising activity of the artemisinin drug derivatives in treating certain types of cancer. However, the reported articles are few, and therefore not statistically significant. The minimal toxicity shown in clinical trials and case reports, along with the selective cytotoxic activity of the compounds, make them possible cancer therapies due to the emerging evidence of the drug’s effectiveness

: manipulation of signaling pathways to inhibit host cell apoptosis

The maintenance of homeostasis in living systems requires the elimination of unwanted cells which is performed, among other mechanisms, by type I cell death or apoptosis. This type of programmed cell death involves several morphological changes such as cytoplasm shrinkage, chromatin condensation (pyknosis), nuclear fragmentation (karyorrhexis), and plasma membrane blebbing that culminate with the formation of apoptotic bodies. In addition to the maintenance of homeostasis, apoptosis also represents an important defense mechanism for cells against intracellular microorganisms. In counterpart, diverse intracellular pathogens have developed a wide array of strategies to evade apoptosis and persist inside cells. These strategies include the manipulation of signaling pathways involved in the inhibition of apoptosis where mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) play a key role. Leishmania is an intracellular protozoan parasite that causes a wide spectrum of diseases known as leishmaniasis. This parasite displays different strategies, including apoptosis inhibition, to down-regulate host cell defense mechanisms in order to perpetuate infection

Characterization of Gene Families Encoding Beta-Lactamases of Gram-Negative Rods Isolated from Ready-to-Eat Vegetables in Mexico City

Beta-lactam resistant bacteria, which are commonly resident in tertiary hospitals, have emerged as a worldwide health problem because of ready-to-eat vegetable intake. We aimed to characterize the genes that provide resistance to beta-lactam antibiotics in Enterobacteriaceae, isolated from five commercial salad brands for human consumption in Mexico City. In total, twenty-five samples were collected, grown in blood agar plates, and the bacteria were biochemistry identified and antimicrobial susceptibility testing was done. The carried family genes were identified by endpoint PCR and the specific genes were confirmed with whole genome sequencing (WGS) by Next Generation Sequencing (NGS). Twelve positive cultures were identified and their microbiological distribution was as follows: 8.3% for Enterobacter aerogene (n = 1), 8.3% for Serratia fonticola (n = 1), 16.7% for Serratia marcesens (n = 2), 16.7% for Klebsiella pneumoniae (n = 2), and 50% (n = 6) for Enterobacter cloacae. The endpoint PCR results showed 11 colonies positive for blaBIL (91.7%), 11 for blaSHV (91.7%), 11 for blaCTX (97.7%), 12 for blaDHA (100%), four for blaVIM (33.3%), two for blaOXA (16.7%), two for blaIMP (16.7%), one for blaKPC (8.3%), and one for blaTEM (8.3%) gen; all samples were negative for blaROB, blaCMY, blaP, blaCFX and blaLAP gene. The sequencing analysis revealed a specific genotype for Enterobacter cloacae (blaSHV-12, blaCTX-M-15, blaDHA-1, blaKPC-2); Serratia marcescens (blaSHV-1, blaCTX-M-3, blaDHA-1, blaVIM-2); Klebsiella pneumoniae (blaSHV-12, blaCTX-M-15, blaDHA-1); Serratia fonticola (blaSHV-12, blaVIM-1, blaDHA-1); and, Enterobacter aerogene (blaSHV-1, blaCTX-M-1, blaDHA-1, blaVIM-2, blaOXA-9). Our results indicate that beta-lactam-resistant bacteria have acquired integrons with a different number of genes that provide pan-resistance to beta-lactam antibiotics, including penicillins, oxacillins, cefalosporins, monobactams, carbapenems, and imipenems

Characterization of Beta-Lactam Resistome of <i>Escherichia coli</i> Causing Nosocomial Infections

Nosocomial infections caused by Escherichia coli pose significant therapeutic challenges due to the high expression of genes encoding antimicrobial drug resistance. In this study, we investigated the conformation of the beta-lactam resistome responsible for the specific pattern of resistance against beta-lactam antibiotics. A total of 218 Escherichia coli strains were isolated from in-hospital patients diagnosed with nosocomial infections, obtained from various sources such as urine (n = 49, 22.48%), vaginal discharge (n = 46, 21.10%), catheter tips (n = 14, 6.42%), blood (n = 13, 5.96%), feces (n = 12, 5.50%), sputum (n = 11, 5.05%), biopsies (n = 8, 3.67%), cerebrospinal fluid (n = 2, 0.92%) and other unspecified discharges (n = 63, 28.90%). To characterize the beta-lactam resistome, all strains were subjected to antibiotic dilution tests and grown in beta-lactam antibiotics supplemented with Luria culture medium. Subsequently, multiplex PCR and next-generation sequencing were conducted. The results show a multi-drug-resistance phenotype, particularly against beta-lactam drugs. The primary determinant of this resistance was the expression of the blaTEM gene family, with 209 positive strains (95.87%) expressing it as a single gene (n = 47, 21.6%) or in combination with other genes. Common combinations included blaTEM + blaCTX (n = 42, 19.3%), blaTEM + blaCTX + blaSHV (n = 13, 6%) and blaTEM + blaCTX + blaBIL (n = 12, 5.5%), among others. The beta-lactam resistome of nosocomial Escherichia coli strains isolated from inpatients at the “October first” Regional Hospital of ISSSTE was predominantly composed of members of the blaTEM gene family, expressed in various configurations along with different members of other beta-lactamase gene families

Apoptosis: Activation and Inhibition in Health and Disease

There are many types of cell death, each involving multiple and complex molecular events. Cell death can occur accidentally when exposed to extreme physical, chemical, or mechanical conditions, or it can also be regulated, which involves a genetically coded complex machinery to carry out the process. Apoptosis is an example of the latter. Apoptotic cell death can be triggered through different intracellular signalling pathways that lead to morphological changes and eventually cell death. This is a normal and biological process carried out during maturation, remodelling, growth, and development in tissues. To maintain tissue homeostasis, regulatory, and inhibitory mechanisms must control apoptosis. Paradoxically, these same pathways are utilized during infection by distinct intracellular microorganisms to evade recognition by the immune system and therefore survive, reproduce and develop. In cancer, neoplastic cells inhibit apoptosis, thus allowing their survival and increasing their capability to invade different tissues and organs. The purpose of this work is to review the generalities of the molecular mechanisms and signalling pathways involved in apoptosis induction and inhibition. Additionally, we compile the current evidence of apoptosis modulation during cancer and Leishmania infection as a model of apoptosis regulation by an intracellular microorganism

The Beta-Lactam Resistome Expressed by Aerobic and Anaerobic Bacteria Isolated from Human Feces of Healthy Donors

Antibiotic resistance is a major health problem worldwide, causing more deaths than diabetes and cancer. The dissemination of vertical and horizontal antibiotic resistance genes has been conducted for a selection of pan-resistant bacteria. Here, we test if the aerobic and anaerobic bacteria from human feces samples in health conditions are carriers of beta-lactamases genes. The samples were cultured in a brain–heart infusion medium and subcultured in blood agar in aerobic and anaerobic conditions for 24 h at 37 °C. The grown colonies were identified by their biochemical profiles. The DNA was extracted and purified by bacterial lysis using thermal shock and were used in the endpoint PCR and next generation sequencing to identify beta-lactamase genes expression (OXA, VIM, SHV, TEM, IMP, ROB, KPC, CMY, DHA, P, CFX, LAP, and BIL). The aerobic bacterias Aeromonas hydrophila, Citrobacter freundii, Proteus mirabilis, Providencia rettgeri, Serratia fonticola, Serratia liquefaciens, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Pantoea agglomerans, Enterococcus faecalis, and Enterobacter cloacae, the anaerobic bacteria: Capnocytophaga species, Bacteroides distasonis, Bifidobacterium adolescentis, Bacteroides ovatus, Bacteroides fragilis, Eubacterium species, Eubacterium aerofaciens, Peptostreptococcus anaerobius, Fusobacterium species, Bacteroides species, and Bacteroides vulgatus were isolated and identified. The results showed 49 strains resistant to beta-lactam with the expression of blaSHV (10.2%), blaTEM (100%), blaKPC (10.2%), blaCYM (14.3%), blaP (2%), blaCFX (8.2%), and blaBIL (6.1%). These data support the idea that the human enteric microbiota constitutes an important reservoir of genes for resistance to beta-lactamases and that such genes could be transferred to pathogenic bacteria