Pathogens, Volume 6, Issue 2 (June 2017) – 13 articles

The goal of this study was to investigate the importance of IgG avidity testing in newborns (NBs) diagnosed with early congenital toxoplasmosis. We collected samples from 88 puerperae infected by Toxoplasma gondii (T. gondii) and their NBs (48 acutely-infected puerperae (AIP) and 40 chronically-infected puerperae (CIP)), from two public maternity hospitals in Goiania city, Goias, Brazil, from 2010 to 2015. Specific anti-T. gondii IgM and IgG serum levels and IgG avidity tests were evaluated using chemiluminescence. Congenital toxoplasmosis was observed in 66.66% (n = 32) of NBs with AIP, 94.1% presenting low avidity (LA) and 51.61% presenting high avidity (HA) test results. The IgG and IgM levels of NBs with LA and their puerperae were higher in comparison with HA NBs and puerperae (p = 0.0001). The avidity tests showed 100% specificity and 50% sensitivity (p = 0.0001). NBs with LA had a 15-fold increased risk of developing congenital toxoplasmosis in comparison with HA NBs. The IgG avidity test could be used to assist in early congenital toxoplasmosis diagnoses in NBs and LA, identifying a greater probability of vertical transmission. Full article

Influenza A viruses (IAV) continually evolve and have the capacity to cause global pandemics. Because IAV represents an ongoing threat, identifying novel therapies and host innate immune factors that contribute to IAV pathogenesis is of considerable interest. This review summarizes the relevant literature as it relates to global host responses to influenza infection at both the proteome and transcriptome level. The various-omics infection systems that include but are not limited to ferrets, mice, pigs, and even the controlled infection of humans are reviewed. Discussion focuses on recent advances, remaining challenges, and knowledge gaps as it relates to influenza-omics infection outcomes. Full article

Herpes simplex virus 1 (HSV-1) uses latency in peripheral ganglia to persist in its human host, however, recurrent reactivation from this reservoir can cause debilitating and potentially life-threatening disease. Most studies of latency use live-animal infection models, but these are complex, multilayered systems and can be difficult to manipulate. Infection of cultured primary neurons provides a powerful alternative, yielding important insights into host signaling pathways controlling latency. However, small animal models do not recapitulate all aspects of HSV-1 infection in humans and are limited in terms of the available molecular tools. To address this, we have developed a latency model based on human neurons differentiated in culture from an NIH-approved embryonic stem cell line. The resulting neurons are highly permissive for replication of wild-type HSV-1, but establish a non-productive infection state resembling latency when infected at low viral doses in the presence of the antivirals acyclovir and interferon-α. In this state, viral replication and expression of a late viral gene marker are not detected but there is an accumulation of the viral latency-associated transcript (LAT) RNA. After a six-day establishment period, antivirals can be removed and the infected cultures maintained for several weeks. Subsequent treatment with sodium butyrate induces reactivation and production of new infectious virus. Human neurons derived from stem cells provide the appropriate species context to study this exclusively human virus with the potential for more extensive manipulation of the progenitors and access to a wide range of preexisting molecular tools. Full article

Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immunodeficiency caused by a loss-of-function mutation in the Signal Transducer and Activator of Transcription 3 (STAT3). This immune disorder is clinically characterized by increased susceptibility to cutaneous and sinopulmonary infections, in particular with Candida and Staphylococcus aureus. It has recently been recognized that the skin microbiome of patients with AD-HIES is altered with an overrepresentation of certain Gram-negative bacteria and Gram-positive staphylococci. However, these alterations have not been characterized at the species- and strain-level. Since S. aureus infections are influenced by strain-specific expression of virulence factors, information on colonizing strain characteristics may provide insights into host-pathogen interactions and help guide management strategies for treatment and prophylaxis. The aim of this study was to determine whether the immunodeficiency of AD-HIES selects for unique strains of colonizing S. aureus. Using multi-locus sequence typing (MLST), protein A (spa) typing, and PCR-based detection of toxin genes, we performed a detailed analysis of the S. aureus isolates (n = 13) found on the skin of twenty-one patients with AD-HIES. We found a low diversity of sequence types, and an abundance of strains that expressed methicillin resistance, Panton-Valentine leukocidin (PVL), and staphylococcal enterotoxins K and Q (SEK, SEQ). Our results indicate that patients with AD-HIES may often carry antibiotic-resistant strains that harbor key virulence factors. Full article

Acute bacterial prostatitis is one of the frequent complications of urinary tract infection (UTI). From the approximately 10% of men having prostatitis, 7% experience a bacterial prostatitis. The purpose of this study was to investigate the prevalence of uropathogens associated with UTIs in older patients with benign prostatic hyperplasia and to assess their susceptibility to commonly prescribed antibiotics as well as the relationships between microbial virulence and resistance features. Uropathogenic Escherichia coli was found to be the most frequent bacterial strain isolated from patients with benign prostatic hyperplasia, followed by Enterococcus spp., Enterobacter spp., Klebsiella spp., Proteus spp., Pseudomonas aeruginosa, and Serratia marcescens. Increased resistance rates to tetracyclines, quinolones, and sulfonamides were registered. Besides their resistance profiles, the uropathogenic isolates produced various virulence factors with possible implications in the pathogenesis process. The great majority of the uropathogenic isolates revealed a high capacity to adhere to HEp-2 cell monolayer in vitro, mostly exhibiting a localized adherence pattern. Differences in the repertoire of soluble virulence factors that can affect bacterial growth and persistence within the urinary tract were detected. The Gram-negative strains produced pore-forming toxins—such as hemolysins, lecithinases, and lipases—proteases, siderophore-like molecules resulted from the esculin hydrolysis and amylases, while Enterococcus sp. strains were positive only for caseinase and esculin hydrolase. Our study demonstrates that necessity of investigating the etiology and local resistance patterns of uropathogenic organisms, which is crucial for determining appropriate empirical antibiotic treatment in elderly patients with UTI, while establishing correlations between resistance and virulence profiles could provide valuable input about the clinical evolution and recurrence rates of UTI. Full article

Toxoplasmosis is caused by infection with the protozoan parasite Toxoplasma gondii. Infections are usually either asymptomatic or develop mild symptoms that are self-limited, but infections in immunosuppressed persons can be severe. Infections in pregnant women can cause serious health problems in the child such as mental retardation and blindness. Infection with T. gondii in immunocompetent adults can lead to impaired eyesight. Toxoplasmosis has ranked very highly in two studies of death and disability attributable to foodborne pathogens. The consumption of raw or undercooked meat containing T. gondii tissue cysts and the consumption of raw vegetables or water contaminated with T. gondii oocysts from cat feces is most frequently associated with human illness. The risk of acquiring a Toxoplasma infection via food varies with cultural and eating habits in different human populations. Full article

Bacteria of genus Achromobacter are emerging pathogens in cystic fibrosis (CF) capable of biofilm formation and development of antimicrobial resistance. Evolutionary adaptions in the transition from primary to chronic infection were assessed by transcriptomic analysis of successive isolates of Achromobacter xylosoxidans from a single CF patient. Several efflux pump systems targeting antimicrobial agents were upregulated during the course of the disease, whereas all genes related to motility were downregulated. Genes annotated to subsystems of sulfur metabolism, protein metabolism and potassium metabolism exhibited the strongest upregulation. K+ channel genes were hyperexpressed, and a putative sulfite oxidase was more than 1500 times upregulated. The transcriptome patterns indicated a pivotal role of sulfur metabolism and electrical signalling in Achromobacter biofilms during late stage CF lung disease. Full article

Although the parasite Toxoplasma gondii is one of the most pervasive neurotropic pathogens in the world, the host-parasite interactions during CNS infection and the consequences of neurological infection are just beginning to be unraveled. The chronic stages of infection have been considered dormant, although several studies have found correlations of infection with an array of host behavioral changes. These may facilitate parasite transmission and impact neurological diseases. During infection, in addition to the presence of the parasites within neurons, host-mediated neuroimmune and hormonal responses to infection are also present. T. gondii induces numerous changes to host neurons during infection and globally alters host neurological signaling pathways, as discussed in this review. Understanding the neurophysiological changes in the host brain is imperative to understanding the parasitic mechanisms and to delineate the effects of this single-celled parasite on health and its contribution to neurological disease. Full article

Enterotoxigenic Escherichia coli (ETEC) causes childhood diarrhea in developing countries. ETEC strains produce the heat-labile enterotoxin (LT) and/or heat-stable enterotoxins (ST) and encode a diverse set of colonization factors used for adherence to intestinal epithelial cells. We previously found that ETEC secretes a heat-stable protein we designated as ETEC Secreted Factor (ESF) that inhibits the extent of NF-κB activation normally induced by tumor necrosis factor alpha (TNF). Here we fractionated ETEC supernatants using fast protein liquid chromatography (FPLC) and determined that ETEC flagellin was necessary and sufficient to protect IκBα from degradation in response to TNF stimulation. These data suggest a potentially novel mechanism by which ETEC may evade the host innate immune response by down-regulating NF-κB-dependent host responses. Full article

Intracellular pathogens have evolved a wide range of strategies to not only escape from the immune systems of their hosts, but also to directly exploit a variety of host factors to facilitate the infection process. One such strategy is to subvert host cell signalling pathways to the advantage of the pathogen. Recent research has highlighted that the human serine/threonine kinase PAK, or p21-activated kinase, is a central component of host-pathogen interactions in many infection systems involving viruses, bacteria, and eukaryotic pathogens. PAK paralogues are found in most mammalian tissues, where they play vital roles in a wide range of functions. The role of PAKs in cell proliferation and survival, and their involvement in a number of cancers, is of great interest in the context of drug discovery. In this review we discuss the latest insights into the surprisingly central role human PAK1 plays for the infection by such different infectious disease agents as viruses, bacteria, and parasitic protists. It is our intention to open serious discussion on the applicability of PAK inhibitors for the treatment, not only of neoplastic diseases, which is currently the primary objective of drug discovery research targeting these enzymes, but also of a wide range of infectious diseases. Full article

Streptococcus suis and group B Streptococcus (GBS) are encapsulated streptococci causing septicemia and meningitis. Antibodies (Abs) against capsular polysaccharides (CPSs) have a crucial protective role, but the structure/composition of the CPS, including the presence of sialic acid, may interfere with the generation of anti-CPS Ab responses. We investigated the features of the CPS-specific Ab response directed against S. suis serotypes 2 and 14 and GBS serotypes III and V after infection or immunization with purified native or desialylated CPSs in mice. Whereas S. suis-infected mice developed a very low/undetectable CPS-specific IgM response, significant anti-CPS IgM titers were measured in GBS-infected animals (especially for type III GBS). No isotype switching was detected in S. suis- or GBS-infected mice. While the expression of sialic acid was essential for the immunogenicity of purified GBS type III CPS, this sugar was not responsible for the inability of purified S. suis types 2, 14 and GBS type V CPSs to induce a specific Ab response. Thus, other biochemical criteria unrelated to the presence of sialic acid may be responsible for the inaptitude of the host immune system to mount an effective response against certain S. suis and GBS CPS types. Full article

Objectives: To evaluate the effectiveness of hydrogen peroxide (HP) use as a disinfectant in the hospital water network for the control of Legionella spp. colonization. Methods: Following the detection of high levels of Legionella contamination in a 136-bed general hospital water network, an HP treatment of the hot water supply (25 mg/L) was adopted. During a period of 34 months, the effectiveness of HP on Legionella colonization was assessed. Legionella was isolated in accordance with ISO-11731 and identification was carried out by sequencing of the mip gene. Results: Before HP treatment, L. pneumophila sg 2–15 was isolated in all sites with a mean count of 9950 ± 8279 cfu/L. After one-month of HP treatment, we observed the disappearance of L. pneumophila 2–15, however other Legionella species previously not seen were found; Legionella pneumophila 1 was isolated in one out of four sampling sites (2000 cfu/L) and other non-pneumophila species were present in all sites (mean load 3000 ± 2887 cfu/L). Starting from September 2013, HP treatment was modified by adding food-grade polyphosphates, and in the following months, we observed a progressive reduction of the mean load of all species (p < 0.05), resulting in substantial disappearance of Legionella colonization. Conclusion: Hydrogen peroxide demonstrated good efficacy in controlling Legionella. Although in the initial phases of treatment it appeared unable to eliminate all Legionella species, by maintaining HP levels at 25 mg/L and adding food-grade polyphosphates, a progressive and complete control of colonization was obtained. Full article

Application of toxic antibacterial agents is considered necessary to control prevalent fresh water microorganisms that grow in evaporative cooling water systems, but can adversely affect the environment and human health. However, natural antibacterial water chemistry has been applied in industrial cooling water systems for over 10 years to inhibit microorganisms with excellent results. The water chemistry method concentrates natural minerals in highly-softened water to produce elevated pH and dissolved solids, while maintaining low calcium and magnesium content. The method provides further benefits in water conservation, and generates a small volume of non-toxic natural salt concentrate for cost efficient separation and disposal if required. This report describes the antimicrobial effects of these chemistry modifications in the cooling water environment and the resultant collective inhibition of microbes, biofilm, and pathogen growth. This article also presents a novel perspective of parasitic microbiome functional relationships, including “Trojan Protozoans” and biofilms, and the function of polyvalent metal ions in the formation and inhibition of biofilms. Reducing global dependence on toxic antibacterial agents discharged to the environment is an emerging concern due to their impact on the natural microbiome, plants, animals and humans. Concurrently, scientists have concluded that discharge of antibacterial agents plays a key role in development of pathogen resistance to antimicrobials as well as antibiotics. Use of natural antibacterial chemistry can play a key role in managing the cooling water environment in a more ecologically sustainable manner. Full article