Strategies of Intracellular Pathogens for Obtaining Iron from the Environment

Most microorganisms are destroyed by the host tissues through processes that usually involve phagocytosis and lysosomal disruption. However, some organisms, called intracellular pathogens, are capable of avoiding destruction by growing inside macrophages or other cells. During infection with intracellular pathogenic microorganisms, the element iron is required by both the host cell and the pathogen that inhabits the host cell. This minireview focuses on how intracellular pathogens use multiple strategies to obtain nutritional iron from the intracellular environment in order to use this element for replication. Additionally, the implications of these mechanisms for iron acquisition in the pathogen-host relationship are discussed

Parasiticidal effect of synthetic bovine Lactoferrin peptides on the enteric parasite Giardia intestinalis

Giardia intestinalis is the most common infectious protozoan parasite in children. Despite the effectiveness of some drugs, the disease remains a major worldwide problem. Consequently, the search for new treatments is important for disease eradication. Biological molecules with antimicrobial properties represent a promising alternative to combat pathogens. Bovine lactoferrin (bLF) is a key component of the innate host defense system, and its peptides have exhibited strong antimicrobial activity. Based on these properties, we evaluated the parasiticidal activity of these peptides on G. intestinalis. Trophozoites were incubated with different peptide concentrations for different periods of time, and the growth or viability was determined by carboxyfluorescein-succinimidyl-diacetate-ester (CFDA) and propidium iodide (PI) staining. Endocytosis of peptides was investigated by confocal microscopy, damage was analyzed by transmission and scanning electron microscopy, and the type of programmed cell death was analyzed by flow cytometry. Our results showed that the LFpeptides had giardicidal activity. The LFpeptides interacted with G. intestinalis and exposure to LFpeptides correlated with an increase in the granularity and vacuolization of the cytoplasm. Additionally, the formation of pores, extensive membrane disruption, and programmed cell death was observed in trophozoites treated with LFpeptides. Our results demonstrate that LFpeptides exhibit potent in vitro antigiardial activity.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Bovine Lactoferrin and Lactoferrin-Derived Peptides Inhibit the Growth of Vibrio cholerae and Other Vibrio species

Vibrio is a genus of Gram-negative bacteria, some of which can cause serious infectious diseases. Vibrio infections are associated with the consumption of contaminated food and classified in Vibrio cholera infections and non-cholera Vibrio infections. In the present study, we investigate whether bovine lactoferrin (bLF) and several synthetic peptides corresponding to bLF sequences, are able to inhibit the growth or have bactericidal effect against V. cholerae and other Vibrio species. The antibacterial activity of LF and LF-peptides was assessed by kinetics of growth or determination of colony forming unit in bacteria treated with the peptides and antibiotics. To get insight in the mode of action, the interaction between bLF and bLF-peptides (coupled to FITC) and V. cholera was evaluated. The damage of effector-induced bacterial membrane permeability was measured by inclusion of the fluorescent dye propidium iodide using flow cytometry, whereas the bacterial ultrastructural damage in bacteria treated was observed by transmission electron microscopy. The results showed that bLF and LFchimera inhibited the growth of the V. cholerae strains; LFchimera permeabilized the bacteria which membranes were seriously damaged. Assays with a multidrug-resistant strain of Vibrio species indicated that combination of sub-lethal doses of LFchimera with ampicillin or tetracycline strongly reduced the concentration of the antibiotics to reach 95% growth inhibition. Furthermore, LFchimera were effective to inhibit the V. cholerae counts and damage due to this bacterium in a model mice. These data suggest that LFchimera and bLF are potential candidates to combat the V. cholerae and other multidrug resistant Vibrio species

<em>Piper betel</em> Compounds Piperidine, Eugenyl Acetate, and Chlorogenic Acid Are Broad-Spectrum Anti-<em>Vibrio</em> Compounds that Are Also Effective on MDR Strains of the Pathogen

The natural population of the aquatic environment supports a diverse aquatic biota and a robust seafood industry. However, this environment also provides an appropriate niche for the growth of pathogenic bacteria that cause problems for human health. For example, species of the genus Vibrio inhabit marine and estuarine environments. This genus includes species that are pathogenic to aquaculture, invertebrates, and humans. In humans, they can cause prominent diseases like gastroenteritis, wound infections, and septicemia. The increased number of multidrug resistant (MDR) Vibrio strains has drawn the attention of the scientific community to develop new broad-spectrum antibiotics. Hence, in this paper we report the bactericidal effects of compounds derived from Piper betel plants: piperidine, chlorogenic acid, and eugenyl acetate, against various strains of Vibrio species. The different MIC90 values were approximately in a range of 2–6 mg/mL, 5–16 mg/mL, 5–20 mg/mL, and 30–80 mg/mL, for piperidine, chlorogenic acid, and eugenyl acetate, respectively. Piperidine showed the best anti-Vibrio effect against the five Vibrio species tested. Interestingly, combinations of sub-inhibitory concentrations of piperidine, chlorogenic acid, and eugenyl acetate showed inhibitory effects in the Vibrio strains. Furthermore, these compounds showed synergism or partial synergism effects against MDR strains of the Vibrio species when they were incubated with antibiotics (ampicillin and chloramphenicol)

Association of <i>PCSK1</i> and <i>PPARG1</i> Allelic Variants with Obesity and Metabolic Syndrome in Mexican Adults

Metabolic diseases, including obesity, diabetes, and metabolic syndrome, are among the most important public health challenges worldwide. Metabolic diseases are classified as multifactorial diseases in which genetic variants such as single-nucleotide polymorphisms (SNPs) may play an important role. The present study aimed to identify associations linking allelic variants of the PCSK1, TMEM18, GPX5, ZPR1, ZBTB16, and PPARG1 genes with anthropometric and biochemical traits and metabolic diseases (obesity or metabolic syndrome) in an adult population from northwestern Mexico. Methods: Blood samples were collected from 523 subjects, including 247 with normal weight, 276 with obesity, and 147 with metabolic syndrome. Anthropometric and biochemical characteristics were recorded, and single-nucleotide polymorphisms (SNPs) were genotyped by real-time PCR. Results: PCSK1 was significantly (p GPX5 was significantly associated with HDL cholesterol levels. In addition, PCSK1 was associated with obesity (p = 1.0 × 10−4) and metabolic syndrome (p = 3.0 × 10−3), whereas PPARG1 was associated with obesity (p = 0.044). Conclusions: The associations found in this study, mainly between allelic variants of PCSK1 and metabolic traits, obesity, and metabolic syndrome, may represent a risk for developing metabolic diseases in adult subjects from northwestern Mexico

Outbreak of Serratia marcescens in the Neonatal Intensive Care Unit of a Tertiary Care Hospital in Mexico

Introduction. We describe an outbreak of Serratia marcescens (S. marcescens) infection in the neonatal intensive care unit at Women’s Hospital in Sinaloa, Mexico. Methods. In April 2021, an outbreak of S. marcescens infection was identified. A case was identified as any patient who tested positive for S. marcescens and showed signs of an infectious process. Results. S. marcescens was isolated from the blood cultures of 15 neonates with clinical signs of neonatal sepsis. Statistical analysis showed that all neonates had an invasive medical device. The problem was controlled after hospital hygiene and sanitation measures were strengthened. Conclusion. The study provides evidence of an outbreak of nosocomial bacteremia due to the cross-transmission of S. marcescens. The findings highlight the need for hospitals to implement strict hygiene measures, especially regarding hand washing, to prevent future outbreaks

Exoproteome and Secretome Derived Broad Spectrum Novel Drug and Vaccine Candidates in <em>Vibrio cholerae</em> Targeted by <em>Piper betel</em> Derived Compounds

<div><p><em>Vibrio cholerae</em> is the causal organism of the cholera epidemic, which is mostly prevalent in developing and underdeveloped countries. However, incidences of cholera in developed countries are also alarming. Because of the emergence of new drug-resistant strains, even though several generic drugs and vaccines have been developed over time, <em>Vibrio</em> infections remain a global health problem that appeals for the development of novel drugs and vaccines against the pathogen. Here, applying comparative proteomic and reverse vaccinology approaches to the exoproteome and secretome of the pathogen, we have identified three candidate targets (<em>ompU</em>, <em>uppP</em> and <em>yajC</em>) for most of the pathogenic <em>Vibrio</em> strains. Two targets (<em>uppP</em> and <em>yajC</em>) are novel to <em>Vibrio</em>, and two targets (<em>uppP</em> and <em>ompU</em>) can be used to develop both drugs and vaccines (dual targets) against broad spectrum <em>Vibrio</em> serotypes. Using our novel computational approach, we have identified three peptide vaccine candidates that have high potential to induce both B- and T-cell-mediated immune responses from our identified two dual targets. These two targets were modeled and subjected to virtual screening against natural compounds derived from <em>Piper betel</em>. Seven compounds were identified first time from <em>Piper betel</em> to be highly effective to render the function of these targets to identify them as emerging potential drugs against <em>Vibrio</em>. Our preliminary validation suggests that these identified peptide vaccines and <em>betel</em> compounds are highly effective against <em>Vibrio cholerae</em>. Currently we are exhaustively validating these targets, candidate peptide vaccines, and <em>betel</em> derived lead compounds against a number of <em>Vibrio</em> species.</p> </div

Protein-protein and host-pathogen interactions among ten preliminary identified <i>Vibrio</i> targets.

<p>The interactions demonstrate that the finally selected three targets (<i>ompU</i>, <i>yajC</i>, and <i>uppP</i>) are involved in <i>Vibrio</i> pathogenesis and modulate host response (immunity and apoptosis) by interacting with the host protein PDCD6.</p