Pathogens — Open Access Journal

Helicobacter pylori (H. pylori) represents an independent risk factor for Gastric Cancer (GC). First Degree Relatives (FDR) of GC subjects and Autoimmune Gastritis (AG) patients are both at increased risk for GC. H. pylori genetic heterogeneity within the gastric niche of FDR and AG individuals has been little explored. To understand whether they exploit an increased H. pylori stability and virulence, 14 AG, 25 FDR, 39 GC and 13 dyspeptic patients (D) were investigated by a cultural PCR-based approach characterizing single colonies-forming-units. We chose three loci within the Cytotoxin-associated gene-A Pathogenicity Island (CagPAI) (cagA,cagE,virB11), vacA, homA and homB as markers of virulence with reported association to GC. Inflammatory/precancerous lesions were staged according to Sydney System. When compared to D, FDR, similarly to GC patients, were associated to higher atrophy (OR = 6.29; 95% CI):1.23–31.96 in FDR; OR = 7.50; 95% CI:1.67–33.72 in GC) and a lower frequency of mixed infections (OR = 0.16; 95% CI:0.03–0.81 in FDR; OR = 0.10; 95% CI:0.02–0.48 in GC). FDR presented also an increased neutrophil infiltration (OR = 7.19; 95% CI:1.16–44.65). Both FDR and GC carried a higher proportion of CagPAI⁺vacAs1i1mx⁺homB⁺ profiles (OR = 2.71; 95% CI: 1.66–4.41 and OR = 3.43; 95% CI: 2.16–5.44, respectively). Conversely, AG patients presented a lower frequency of subtypes carrying a stable CagPAI and vacAs1i1mx. These results underline different H. pylori plasticity in FDR and AG individuals, and thus, a different host-bacterium interaction capacity that should be considered in the context of eradication therapies. Full article

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). Full article

Hepatitis B virus (HBV) is an enveloped partial double-stranded DNA virus that can cause acute and chronic hepatitis. According to the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), 257 million people are living with HBV. Moreover, 20,900 acute hepatitis B cases were reported in 2016. Hepatitis B is highly prevalent in the African, Western Pacific, Eastern Mediterranean, South-East Asia, and European regions, respectively. Due to the high mutational rate of HBV and lack of reverse transcriptase proofreading activity, ten different genotypes with different geographical distributions have been identified. HBV pathogenesis and severity of infection depend on several host and viral factors, particularly, the genetic variability of both the host and virus. Although HBV infection is a global health concern, there is a lack of adequate studies and reports in the Middle East and North Africa (MENA) region. Here, we provide a review on HBV epidemiology, pathogenesis, host–pathogen interactions, coinfection with selected viruses, and laboratory diagnosis, focusing on studies conducted in the MENA region to determine the current situation of the HBV infection and outline the future study areas. Full article

In August 2015, Malaysia experienced an outbreak of acute respiratory disease in racehorses. Clinical signs observed were consistent with equine influenza (EI) infection. The index cases were horses recently imported from New Zealand. Rapid control measures, including temporary cancellation of racing, were implemented to minimize the impact of the outbreak. By November, the disease outbreak was resolved, and movement restrictions were lifted. The aim of this study was to confirm the clinical diagnosis and characterize the causal virus. A pan-reactive influenza type A real-time RT-PCR was used for confirmatory diagnosis. Antigenic characterization by haemagglutinin inhibition using a panel of specific ferret antisera indicated that the causal virus belonged to clade 1 of the H3N8 Florida sub-lineage. The genetic characterization was achieved by the whole genome sequencing of positive nasal swabs from clinically affected animals. Pylogenetic analysis of the haemagglutinin (HA) and neuraminidase (NA) genes demonstrated ≥99% homology with several EI strains that had recently circulated in the USA and Japan. The antigenic and genetic characterization did not indicate that the current World Organisation for Animal Health (OIE) recommendations for EI vaccine composition required modification. Full article

This study was performed to investigate the mechanism of action of ursolic acid in terms of anti-Toxoplasma gondii effects, including immunomodulatory effects. We evaluated the anti-T. gondii effects of ursolic acid, and analyzed the production of nitric oxide (NO), reactive oxygen species (ROS), and cytokines through co-cultured immune cells, as well as the expression of intracellular organelles of T. gondii. The subcellular organelles and granules of T. gondii, particularly rhoptry protein 18, microneme protein 8, and inner membrane complex sub-compartment protein 3, were markedly decreased when T. gondii was treated with ursolic acid, and their expressions were effectively inhibited. Furthermore, ursolic acid effectively increased the production of NO, ROS, interleukin (IL)-10, IL-12, granulocyte macrophage colony stimulating factor (GM-CSF), and interferon-β, while reducing the expression of IL-1β, IL-6, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-β1) in T. gondii-infected immune cells. These results demonstrate that ursolic acid not only causes anti-T. gondii activity/action by effectively inhibiting the survival of T. gondii and the subcellular organelles of T. gondii, but also induces specific immunomodulatory effects in T. gondii-infected immune cells. Therefore, this study indicates that ursolic acid can be effectively utilized as a potential candidate agent for developing novel anti-toxoplasmosis drugs, and has immunomodulatory activity. Full article

Diarrhoeal disease is still one of the most challenging issues for health in many countries across the Eastern Mediterranean region (EMR), with infectious diarrhoea being an important cause of morbidity and mortality, especially in children under five years of age. However, the understanding of the aetiological spectrum and the burden of enteric pathogens involved in diarrhoeal disease in the EMR is incomplete. Non-typhoidal Salmonella (NTS), the focus of this review, is one of the most frequently reported bacterial aetiologies in diarrhoeal disease in the EMR. Strains of NTS with resistance to antimicrobial drugs are increasingly reported in both developed and developing countries. In the EMR, it is now widely accepted that many such resistant strains are zoonotic in origin and acquire their resistance in the food-animal host before onward transmission to humans through the food chain. Here, we review epidemiological and microbiological aspects of diarrhoeal diseases among children in the EMR, with emphasis on the implication and burden of NTS. We collate evidence from studies across the EMR on the zoonotic exposure and antimicrobial resistance in NTS at the interface between human and foods of animal origin. This review adds to our understanding of the global epidemiology of Salmonella with emphasis on the current situation in the EMR. Full article

Periodontitis is a highly prevalent infectious disease that affects ~ 50% of the adults in the USA alone. Two Gram-positive anaerobic oral bacteria, Filifactor alocis and Peptoanaerobacterstomatis, have emerged as important periodontal pathogens. Neutrophils are a major component of the innate host response in the gingival tissue, and the contribution of neutrophil-derived cytokines and chemokines plays a central role in disease progression. The pattern of cytokines and chemokines released by human neutrophils upon stimulation with newly appreciated periodontal bacteria compared to the keystone oral pathogen Porphyromonas gingivalis was investigated. Our results showed that both F. alocis and P. stomatis triggered TLR2/6 activation. F. alocis induced significant changes in gene expression of cytokines and chemokines in human neutrophils compared to unstimulated cells. However, except for IL-1ra, neutrophils released lower levels of cytokines and chemokines in response to F. alocis compared to P. stomatis. Furthermore, bacteria-free conditioned supernatant collected from neutrophils challenged with P. stomatis, but not from P. gingivalis or F. alocis, was chemotactic towards both neutrophils and monocytes. Elucidating stimuli-specific modulation of human neutrophil effector functions in the context of dysbiotic microbial community constituents provides valuable information for understanding the pathogenesis of periodontal diseases. Full article

Toxoplasma gondii is an obligate apicomplexan zoonotic parasite that infects humans and other animals and is responsible for toxoplasmosis. This parasite causes one of the most common parasitic infections in humans worldwide. Toxoplasmosis meets the requirements for a One Health Disease due to its ability to affect the health of human beings as well as domestic and free ranging animals. Integrating human, domestic animal, and wildlife data could better assess the risk and devise methods of control. A first step of such an approach would be the knowledge of the prevalence of parasitosis in humans and animals in selected areas. Therefore, the aim of the present study was to evaluate the occurrence of Toxoplasma infection in 216 free ranging birds belonging to different genera/species by serology and molecular techniques. Twenty-five out of 216 animals (11.6%) were positive to the immunofluorescence antibody test (IFAT) with antibody titers ranging from 1/20 to 1/320, and 19 of them (8.8%) also showed a positive PCR for Toxoplasma DNA. The results confirmed the widespread occurrence of Toxoplasma infection in wild birds and serological data were corroborated by molecular results in birds that also had low antibody titers. The knowledge of the wide occurrence of the parasite in game and wild birds should enhance the accurate estimation of the risks in handling, managing, and eating these species with regard to domestic carnivores as well as the impact of viscera and offal in the environment. Full article

High throughput sequencing of total RNA isolated from symptomatic leaves of a sweet cherry tree (Prunus avium cv. 0900 Ziraat) from Turkey identified a new member of the genus Robigovirus designated cherry virus Turkey (CVTR). The presence of the virus was confirmed by electron microscopy and overlapping RT-PCR for sequencing its whole-genome. The virus has a ssRNA genome of 8464 nucleotides which encodes five open reading frames (ORFs) and comprises two non-coding regions, 5′ UTR and 3′ UTR of 97 and 296 nt, respectively. Compared to the five most closely related robigoviruses, RdRp, TGB1, TGB2, TGB3 and CP share amino acid identities ranging from 43–53%, 44–60%, 39–43%, 38–44% and 45–50%, respectively. Unlike the four cherry robigoviruses, CVTR lacks ORFs 2a and 5a. Its genome organization is therefore more similar to African oil palm ringspot virus (AOPRV). Using specific primers, the presence of CVTR was confirmed in 15 sweet cherries and two sour cherries out of 156 tested samples collected from three regions in Turkey. Among them, five samples were showing slight chlorotic symptoms on the leaves. It seems that CVTR infects cherry trees with or without eliciting obvious symptoms, but these data should be confirmed by bioassays in woody and possible herbaceous hosts in future studies. Full article

Taro is an important crop in parts of the world, especially in the Pacific Islands. Like all plants, it is also susceptible to virus infections that could result in diseases, which negatively affects the source of food and trade revenue. Understanding the biology of taro viruses could improve current knowledge regarding the relationship between viruses and taro, thus allowing for a better approach towards the management of the diseases that are associated with them. By compiling and discussing the research on taro and its four major viruses (Dasheen mosaic virus, Taro bacilliform virus, Colocasia bobone disease virus, and Taro vein chlorosis virus) and a relatively new one (Taro bacilliform CH virus), this paper explores the details of each virus by examining their characteristics and highlighting information that could be used to mitigate taro infections and disease management. Full article

The gram-negative bacterial pathogen Pseudomonas aeruginosa represents a prominent clinical concern. Due to the observed high levels of antibiotic resistance, copious biofilm formation, and wide array of virulence factors produced by these bacteria, new treatment technologies are required. Here, we present the development of a series of P. aeruginosa LecA-targeted polymeric nanoparticles and demonstrate the anti-adhesion and biofilm inhibitory properties of these constructs. Full article

The field of IL-17 biology has received much attention over the last decade owing to the pathogenic role of this cytokine in psoriasis and other autoinflammatory disorders and the successful implementation of IL-17-targeting therapies in patients suffering from these diseases. IL-17-mediated pathologies are contrasted by the important host beneficial effects of this cytokine. IL-17 is essential for regulating microbial colonization in barrier tissues. Rare congenital defects in the IL-17 pathway exemplify the relevance of IL-17 in protective immunity against the opportunistic fungal pathogen C. albicans. However, more recently, evidence is accumulating that IL-17 can also provide protection against fungi other than C. albicans. Importantly, protective IL-17 responses directed against commensal fungi can, under certain conditions, promote inflammation with detrimental consequences for the host, thereby assigning fungi a new role as disease-promoting factors apart from their role as potential infectious agents. Full article

Flexible adaptation to the host environment is a critical trait that underpins the success of numerous microbes. The polymorphic fungus Candida albicans has evolved to persist in the numerous challenging niches of the human body. The interaction of C. albicans with a mucosal surface is an essential prerequisite for fungal colonisation and epitomises the complex interface between microbe and host. C. albicans exhibits numerous adaptations to a healthy host that permit commensal colonisation of mucosal surfaces without provoking an overt immune response that may lead to clearance. Conversely, fungal adaptation to impaired immune fitness at mucosal surfaces enables pathogenic infiltration into underlying tissues, often with devastating consequences. This review will summarise our current understanding of the complex interactions that occur between C. albicans and the mucosal surfaces of the human body. Full article

Pneumocystis is a ubiquitous atypical fungus that is distributed globally. The genus comprises morphologically similar but genetically heterogeneous species that have co-evolved with specific mammalian hosts as obligate intra-pulmonary pathogens. In humans, Pneumocystis jirovecii is the causative organism of Pneumocystis pneumonia (PCP) in immunocompromised individuals, a serious illness frequently leading to life-threatening respiratory failure. Initially observed in acquired immunodeficiency syndrome (AIDS) patients, PCP is increasingly observed in immunocompromised non-AIDS patients. The evolving epidemiology and persistently poor outcomes of this common infection will require new strategies for diagnosis and treatment. A deeper understanding of host immune responses and of the cells that mediate them will improve the chance of developing new treatment strategies. This brief review provides an update on recent studies on the role of host immunity against Pneumocystis. Full article

Salmonellosis is one of the major public health concerns in Bahrain as it has increased rapidly during the past few years. This study aims to determine the prevalence of salmonellosis in children and the possible risk factors such as age, geographical area, nationality, gender, unsafe drinking water, infant born weight and gastrointestinal disease. The cases of salmonellosis in children reported by the Ministry of Health of Bahrain ranged from 21 to 26 per 100,000 population during the period 2012–2016. Salmonellosis cases were geographically concentrated in the capital and northern regions. Statistical analysis showed a significant difference in the number of salmonellosis cases between Bahrainis and non-Bahrainis based on region, and gender (p < 0.001). In the Bahraini cohort, there was an association between the increase of cases and the number of gastrointestinal disease-related deaths (p < 0.05). In addition, unsafe water (over the level of 2.14%) and low-birth weight (<3.100 g) were associated, but not statistically significant (p = 0.086 and p = 0.126, respectively) with the increase of salmonellosis cases. Despite the decline in the number of cases, the results of this study contribute to the understanding of the epidemiology of Salmonella in humans and this, in turn, will help develop and implement preventative measures. Full article

Zoonoses present a major public health threat and are estimated to account for a substantial part of the infectious disease burden in low-income countries. The severity of zoonotic diseases is compounded by factors such as poverty, living in close contact with livestock and wildlife, immunosuppression as well as coinfection with other diseases. The interconnections between humans, animals and the environment are essential to understand the spread and subsequent containment of zoonoses. We searched three scientific databases for articles relevant to the epidemiology of bacterial zoonoses/zoonotic bacterial pathogens, including disease prevalence and control measures in humans and multiple animal species, in various African countries within the period from 2008 to 2018. The review identified 1966 articles, of which 58 studies in 29 countries met the quality criteria for data extraction. The prevalence of brucellosis, leptospirosis, Q fever ranged from 0–40%, 1.1–24% and 0.9–28.2%, respectively, depending on geographical location and even higher in suspected outbreak cases. Risk factors for human zoonotic infection included exposure to livestock and animal slaughters. Dietary factors linked with seropositivity were found to include consumption of raw milk and locally fermented milk products. It was found that zoonoses such as leptospirosis, brucellosis, Q fever and rickettsiosis among others are frequently under/misdiagnosed in febrile patients seeking treatment at healthcare centres, leading to overdiagnoses of more familiar febrile conditions such as malaria and typhoid fever. The interactions at the human–animal interface contribute substantially to zoonotic infections. Seroprevalence of the various zoonoses varies by geographic location and species. There is a need to build laboratory capacity and effective surveillance processes for timely and effective detection and control of zoonoses in Africa. A multifaceted ‘One Health’ approach to tackle zoonoses is critical in the fight against zoonotic diseases. The impacts of zoonoses include: (1) Humans are always in contact with animals including livestock and zoonoses are causing serious life-threatening infections in humans. Almost 75% of the recent major global disease outbreaks have a zoonotic origin. (2) Zoonoses are a global health challenge represented either by well-known or newly emerging zoonotic diseases. (3) Zoonoses are caused by all-known cellular (bacteria, fungi and parasites) and noncellular (viruses or prions) pathogens. (4) There are limited data on zoonotic diseases from Africa. The fact that human health and animal health are inextricably linked, global coordinated and well-established interdisciplinary research efforts are essential to successfully fight and reduce the health burden due to zoonoses. This critically requires integrated data from both humans and animals on zoonotic diseases. Full article

Enterobacter cloacae complex has been increasingly recognized as a nosocomial pathogen representing the third major Enterobacteriaceae species involved with infections. This study aims to evaluate virulence and antimicrobial susceptibility of subpopulations generated from macrocolonies of NDM-1 producing Enterobacter hormaechei clinical isolates. Biofilm was quantified using crystal violet method and fimbrial genes were investigated by PCR. Susceptibility of antimicrobials, alone and combined, was determined by minimum inhibitory concentration and checkerboard assays, respectively. Virulence and efficacy of antimicrobials were evaluated in Galleria mellonella larvae. Importantly, we verified that some subpopulations that originate from the same macrocolony present different biofilm production ability and distinct susceptibility to meropenem due to the loss of bla_NDM-1 encoding plasmid. A more in-depth study was performed with the 798 macrocolony subpopulations. Type 3 fimbriae were straightly related with biofilm production; however, virulence in larvae was not statistically different among subpopulations. Triple combination with meropenem–rifampicin–polymyxin B showed in vitro synergistic effect against all subpopulations; while in vivo this treatment showed different efficacy rates for 798-1S and 798-4S subpopulations. The ability of multidrug resistant E. hormaechei isolates in generating bacterial subpopulations presenting different susceptible and virulence mechanisms are worrisome and may explain why these infections are hardly overcome. Full article

Naturally acquired chicken anemia virus (CAV) infection in chickens frequently occurs from 3 weeks of age onward after maternally derived antibodies have decayed. The oral inoculation of older chickens with CAV was reported to have negative effects on cell-mediated immune function, and pathological changes were identified. To date, there has been no complete illustration of an immunological and persistent infection. To understand the pathogenesis of persistent CAV infection, an immunological study of CAV-infected 3-week-old specific pathogen-free (SPF) chickens was carried out by different routes of inoculation. The weight, packed cell volumes, and organ samples were obtained at 7, 14, 21, and 28 days postinfection (dpi). Here, we compared hematological, immunological, and sequential pathological evaluations and determined the CAV tissue distribution in different organs. Neither a reduction in weight gain nor anemia was detected in either the inoculated or the control group. The immune-pathological changes were investigated by evaluating the body and thymus weight ratio and specific antibody titer. Delayed recovery of the thymus corresponding to a low antibody response was detected in the orally inoculated group. This is different from what was found in chickens intramuscularly infected with the same dose of CAV. The CAV remaining in a wide range of tissues was examined by viral reisolation into cell culture. The absence of the virus in infected tissues was typically found in the intramuscularly inoculated group. These chickens were immediately induced for a protective antibody response. A few viruses replicating in the thymus were found 21 dpi due to the regression in the antibody titer in the orally inoculated group. Our findings support that a natural infection with CAV may lead to the gradual CAV viral replication in the thymus during inadequate antibody production. The results clearly confirmed that virus-specific antibodies were essential for viral clearance. Under CIA-risk circumstances, administration of the CAV vaccine is important for achieving a sufficient protective immune response. Full article

Apicomplexan parasites are protozoan organisms that are characterised by complex life cycles and they include medically important species, such as the malaria parasite Plasmodium and the causative agents of toxoplasmosis (Toxoplasma gondii) and cryptosporidiosis (Cryptosporidium spp.). Apicomplexan parasites can infect one or more hosts, in which they differentiate into several morphologically and metabolically distinct life cycle stages. These developmental transitions rely on changes in gene expression. In the last few years, the important roles of different members of the ApiAP2 transcription factor family in regulating life cycle transitions and other aspects of parasite biology have become apparent. Here, we review recent progress in our understanding of the different members of the ApiAP2 transcription factor family in apicomplexan parasites. Full article