Challenge Infection Research Articles

Prolonged immune response to tick-borne Ehrlichia chaffeensis infection using a genetically modified live vaccine.

Ehrlichia chaffeensis, a tick transmitted rickettsial bacterium, causes monocytic ehrlichiosis in humans and dogs. Earlier, we demonstrated that dogs immunized with a mutant strain of E. chaffeensis having a functional disruption in the gene encoding the phage head-to-tail connector protein serves as a modified live vaccine (MLAV) capable of inducing immunity against intravenous and tick-transmitted infection challenges within one month of vaccination. In this follow-up investigation, we assessed the duration of MLAV-induced immunity for one-year period against tick-transmission infection challenge. Dogs vaccinated with the MLAV were subsequently exposed to wild-type E. chaffeensis via tick transmission at 4-, 8-, and 12-months post-vaccination. Unvaccinated controls showed higher infection rates during the one-month assessment following infection. In contrast, MLAV-immunized dogs rapidly cleared infections and exhibited significantly fewer systemic bacterial infections compared to unvaccinated controls. Robust E. chaffeensis-specific IgG and CD4 T-cell responses persisted throughout the assessment period. Our findings underscore the efficacy of MLAV in providing natural hosts with protection against E. chaffeensis infection for up to one year following infected tick exposure.

Potential of vB_Pa_ZCPS1 phage embedded in situ gelling formulations as an ocular delivery system to attenuate Pseudomonas aeruginosa keratitis in a rabbit model.

Pseudomonas aeruginosa keratitis (or pink eye) is a challenging ocular infection that causes serious complications due to the deficiency of effective antibiotic treatment. Thus, in this study we isolated and characterized a specific bacteriophage, phage vB_Pa_ZCPS1, to be used to formulate an in situ- gel loaded bacteriophage for an in vivo rabbit infection treatment model. Phage vB_Pa_ZCPS1 is a double-stranded DNA bacterial virus, of 46,135 bp encoding 75 open reading frames (ORFs) with no antibiotic resistance genes detected. Moreover, it has a podoviral morphotype from the Caudoviricetes class with a 62.4 nm capsid and a short inflexible tail of around 18.8 nm, as indicated by the transmission electron microscope (TEM). Phage vB_Pa_ZCPS1 presented good stability to the UV exposure and a wide range of pH values from 3.0 to 11.0. In addition, the phage-bacteria dynamics study showed that phage vB_Pa_ZCPS1 was effective against P. aeruginosa, especially at low multiplicities of infections (MOIs), including 0.001, 0.01, and 0.1. Respectively, it was loaded to the characterized in situ gel composed of 14 % Pluronic F-127 and 1.5 % HPMC K4M polymer. The in situ-gel has a gelling time of 30 s ± 1, and a temperature of 33 °C ± 1, where the viscosity of the gel increases 10-fold. For the in vivo trial, the infected group treated with phage presented improved clinical outcomes, where the histopathological analysis revealed normal corneal thickness and intact corneal stratified squamous epithelium. Thus, the in situ-gel loaded phage vB_Pa_ZCPS1 could be a potential candidate approach to treat P. aeruginosa keratitis.

P-300. Antimicrobial Resistance Focus in French ICU: A national surveillance network analysis on Pseudomonas aeruginosa nosocomial infections

Abstract Background The aim of this study was to perform a comprehensive description on a cohort of Pseudomonas aeruginosa infected patients in ICU, comparing their characteristics between susceptible and resistant strains, to understand the impact of resistance on clinical decisions and to characterize patients at risk of MDR. Site of infection of Pseudomonas aeruginosa Methods Adult patients hospitalized in France for at least 48 hours in ICU participating to REA-REZO surveillance between 2018 and 2021 were included in the data base used to create this cohort. Resistance patterns of Pseudomonas aeruginosa Results 4196 patients with nosocomial Pseudomonas aeruginosa infections were included in this cohort. Most infections were identified in patients with pneumonia, with a consistently high prevalence ranging from 71.5% to 74.5% depending on the year. Among the Pseudomonas, 1734 (31.0%) were resistant to piperacillin/tazobactam, 1331 (23.8%) were resistant to ceftazidime, and 1191 (21.3%) were carbapenem resistant. A statistically significant difference (p< 0.001) in resistance patterns between the first and subsequent infections is seen, notably for resistance to carbapenems which rose markedly from initial to subsequent infections, from 16.3% to 27.8% (p< 0.001). Regarding occurrence of resistant Pseudomonas strains, statistically significant differences in age distribution among the resistance groups are noted (p< 0.001), particularly evident in patients under 55, where 24.0% of those with dual resistance are under this age threshold, compared to 19.7% with no resistance. The SAPS II score was higher among resistant strains, as well as the duration in ICU stay, suggesting more challenging infections. Description of the patient with Pseudomonas aeruginosa infections Conclusion These results reaffirm the critical challenge posed by resistant Pseudomonas in the ICU. It highlights the need for comprehensive antibiotic strategies that address the clinical, psychological, and economic dimensions of this issue. Disclosures Xavier Bourge, PharmD, MSD France: Employee Arnaud Friggeri, MD, MSD France: Advisor/Consultant Alain Lepape, MD, MSD France: Grant/Research Support Claire Prevot, n/a, MSD France: Employee Anais Machut, n/a, MSD France: Grant/Research Support Charles-Hervé Vacheron, MD, MSD France: Grant/Research Support

P-65. Results from A Phase 2 Clinical Trial for Treatment of Bone And Joint Infections with Afabicin, A First-in-Class Selective Anti-Staphylococcal Antibiotic

Abstract Background Staphylococci are the most common causative pathogens in bone and joint infections (BJI). Treatment for BJI is a major clinical challenge, with recurrent and persistent infections occurring in 40% of patients. Afabicin is the most advanced FabI inhibitor in clinical development and has the potential to be the first microbiome-sparing anti-staphylococcal antibiotic. Currently, a Phase 2 trial in BJI (NCT03723551) is enrolling patients to be treated for 3-6 weeks with afabicin or standard of care (SoC). Results of the first cohort in this study (2-3 weeks treatment) are presented here Methods In an ongoing multicenter, open-label, Phase 2 study, the safety, tolerability, and efficacy of afabicin was compared to those of SoC, in the treatment of patients with BJI. Patients with osteomyelitis, septic arthritis, or prosthetic joint infections were randomized (5 afabicin: 1 SoC) to receive IV and oral treatment for 14 to 21 days. Afabicin treatment (55 mg IV/ 80 mg PO BID) was compared to a pre-defined SoC treatment. Results Twenty patients were included in microbiological intent-to-treat (mITT) population and were treated for up to 21 days with afabicin or SoC (17 afabicin and 3 SoC). The mean treatment duration was 20.1 days for afabicin and 19.7 days for SoC. Overall, osteomyelitis was the most common diagnosis (85%). The most frequent baseline pathogen was Staphylococcus aureus (19 patients), and 18 patients had methicillin-sensitive S. aureus. All 20 patients were treatment responders at End of Treatment (EoT) visit. The clinical response at 4 weeks post EoT was 13 of 15 patients in the afabicin arm, consistent with patient exposure being above PK/PD targets derived from non-clinical modeling. All 3 patients in the SOC arm achieved clinical response at 4 weeks post EoT. At 12 weeks post EoT, the clinical response rate was 13 of 15 patients in the afabicin arm and 2 of 3 patients in the SoC arm. A similar safety profile was observed in the afabicin arm versus SoC arm. Conclusion The clinical response rate and safety profile of 2-3 weeks treatment of staphylococcal BJI with afabicin was comparable to SoC. These data support exploring longer durations of treatment in the study. Additionally, the impact of Afabicin on BJI patient’s gut microbiota will be explored. Disclosures Alireza Shamaei Tousi, PhD, Debiopharm International: Salary Moritz Marquardt, n/a, Debiopharm International: Salary Annick Menetrey, n/a, Debiopharm International: Salary Justyna Nowakowska, n/a, Debiopharm International: Salary Justine Dao, n/a, Debiopharm International: Salary David Cameron, PhD, Debiopharm International S.A.: Salary Charlotte Catala-Goldschmidt, n/a, Debiopharm International: Salary Ricardo Chaves, n/a, Debiopharm International S.A.: Salary

P-1438. Health-Related Social Needs and Guardian Adversity in Outpatient Pediatric Infectious Diseases

Abstract Background Infectious Diseases (ID) outpatient settings do not routinely screen for psychosocial needs of patients and families that may exacerbate infectious processes or challenge traditional treatment. We assessed the prevalence of health-related social needs (HRSN), guardian adverse childhood experiences (ACEs), and neighborhood-level socioeconomic deprivation in two pediatric outpatient ID clinics. Methods Using a cross-sectional study design, we approached English- and Spanish-speaking guardians of outpatient ID patients at two campuses. Guardians completed a HRSN screen (evaluating food/housing insecurity, transportation access, and mental health concerns) and the 10-question ACEs questionnaire (evaluating traumatic childhood experiences of guardians). Responses were entered into REDCap. We geocoded street addresses to identify census tract-level socioeconomic deprivation index (SDI) scores, with higher scores indicating more deprivation. We quantified individual HRSN items, total ACE scores, and SDI measures. We extracted clinical/demographic information from patient charts. Descriptive analyses were pursued. ANOVA analyses explored associations with psychosocial needs and SDI scores.Figure 1.Association of SDI score and Food Insecurity Over the Past 12 Months. Results To date, 221 caregivers have been surveyed, and results are described in Table 1. Most children identified as White, non-Hispanic, and English-speaking. Many families reported any food insecurity (15%), regular caregiver depressive symptoms (20%), and recent anxiety (70%). Four percent lived in an unsteady place, and 5% had transportation issues that affected access to medical care. Firearms were present in 35% of homes. Nineteen percent of guardians had high ACEs (≥4). The mean SDI score was 0.32 (range 0.11-0.71), similar to our institution’s primary service area. Higher SDI scores were associated with more food insecurity over the past 12 months (Figure 1, p< 0.001) and the past week (Figure 2, p=0.01).Figure 2.Association of SDI Score and Food Insecurity Over the Past Week. Conclusion Guardians of children receiving ID outpatient care reported HRSNs and ACEs. SDI score may be a useful adjuvant to screening to identify more efficiently those at risk for challenges like food insecurity. Outpatient ID settings can identify and help mitigate these concerns in clinical encounters. Disclosures Elizabeth P. Schlaudecker, MD, MPH, Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant

P-973. Pediatric Infectious Diseases rotation for general pediatric residents in Washington DC: impact, benefits and pitfalls

Abstract Background Although infectious diseases present significant challenges in pediatric care, formal training in pediatric infectious diseases is not mandated in categorical pediatric residency training. This research seeks to examine the self-assessed confidence levels of general pediatric residents in Washington DC in managing common infectious diseases. The study specifically compares the confidence levels of residents who have undergone elective infectious diseases training with those who have not. Subjective Confidence in the Management of Common Infectious Diseases Encounters Methods A cross-sectional study was conducted using voluntary surveys distributed among pediatric residents from various programs in Washington DC. The surveys aimed to assess subjective confidence levels in managing common infectious disease conditions and to explore motivation to pursue infectious disease training. Effect of infectious diseases elective rotation on interest in infectious diseases as a career. Are you more or less likely to pursue infectious diseases fellowship? Results Analysis of 20 completed surveys revealed that residents who completed infectious diseases rotations demonstrated significantly higher confidence levels in managing infectious disease conditions compared to their counterparts (P: < 0.001). Notably, residents with specialized training showed increased confidence in antibiotic selection and in their diagnostic abilities. Additionally, they exhibited enhanced confidence in managing specific presentations such as sexually transmitted diseases, fever of unknown origin, and central nervous system infections (all with P < 0.05). Finally, 22% of respondents expressed an increased likelihood of pursuing a career in infectious diseases following their rotation. Effect of infectious diseases rotation on the confidence in the management of inpatient and outpatient infectious diseases encounters Conclusion These findings underscore the potential benefits of incorporating infectious diseases rotations into pediatric residency programs, as evidenced by improved skills in antibiotic selection, diagnosis, and management of specific infectious disease scenarios. Additionally, the observed increased interest in pursuing a career in infectious diseases among a subset of residents highlights the positive impact of such training on career trajectory and specialty choice. Investigators plan to distribute the questionnaire more broadly across the US to see if these results are more widespread. Disclosures All Authors: No reported disclosures

P-1514. Cefepime-taniborbactam Exhibits Limited Cross-resistance with Ceftazidime-avibactam and Ceftolozane-tazobactam against Carbapenem-nonsusceptible Enterobacterales and Multidrug-resistant Pseudomonas aeruginosa from the United States 2018-2022

Abstract Background Cefepime-taniborbactam (FTB) is an investigational β-lactam/β-lactamase inhibitor combination with activity against most isolates of carbapenem-resistant and multidrug-resistant (MDR) Enterobacterales and P. aeruginosa. We evaluated the activity of FTB and comparators against clinical isolates of Enterobacterales and P. aeruginosa from the US and assessed FTB cross-resistance to ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (CT) in resistant subsets. Methods MICs were determined by CLSI reference broth microdilution against Enterobacterales (n=4,932) and P. aeruginosa (n=1,508) collected in the US in 2018-2022. Phenotypes were based on 2024 CLSI breakpoints. A provisional FTB susceptible breakpoint of ≤16 µg/mL was used for comparative purposes. An MDR phenotype was defined as resistance to ≥1 agent from ≥3 drug classes. Results Among Enterobacterales, 1.8% of isolates were nonsusceptible to meropenem (MEM; Table 1). FTB was the most active agent, inhibiting 96.7% of MEM-nonsusceptible Enterobacterales isolates at ≤16 µg/mL whereas 80.4% were susceptible to CZA and 87.0% were susceptible to meropenem-vaborbactam (MEV). Among P. aeruginosa, 11.9% of isolates were MDR (Table 1). FTB was the most active agent, inhibiting 82.2% of MDR P. aeruginosa isolates at ≤16 µg/mL whereas 56.1% were susceptible to CT and 63.9% were susceptible to CZA (Table 1). Among MEM-nonsusceptible Enterobacterales, 80.2% were susceptible to both FTB and CZA, 16.5% were susceptible to FTB but not to CZA, 1.1% were susceptible to CZA but not to FTB, and 2.2% were nonsusceptible to both agents (Table 2A). Among MDR P. aeruginosa, 54.4% were susceptible to both FTB and CT, 27.8% were susceptible to FTB but not to CT, 1.7% were susceptible to CT but not to FTB, and 16.1% were nonsusceptible to both agents (Table 2B). Conclusion FTB was active in vitro against recent clinical isolates of Enterobacterales and P. aeruginosa from the US including most isolates resistant to CZA and CT in key resistant subsets. These data support continued development of FTB as a potential treatment option for patients with challenging infections due to carbapenem-resistant Enterobacterales and MDR P. aeruginosa. Disclosures Greg Moeck, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Stocks/Bonds (Private Company) Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant

Inferring the energy cost of resistance to parasitic infection and its link to a trade-off

BackgroundIn infected hosts, immune responses trigger a systemic energy reallocation away from energy storage and growth, to fuel a costly defense program. The exact energy costs of immune defense are however unknown in general. Life history theory predicts that such costs underpin trade-offs between host disease resistance and other fitness related traits, yet this has been seldom assessed. Here we investigate immune energy cost induced by infection, and their potential link to a trade-off between host resistance and fat storage that we previously exposed in sheep divergently selected for resistance to a pathogenic helminth.ResultsTo this purpose, we developed a mathematical model of host-parasite interaction featuring individual changes in energy allocation over the course of infection. The model was fitted to data from an experimental infectious challenge in sheep from genetically resistant and susceptible lines to infer the magnitude of immune energy costs. A relatively small and transient immune energy cost in early infection best explained within-individual changes in growth, energy storage and parasite burden. Among individuals, predicted responses assuming this positive energy cost conformed to the observed trade-off between resistance and storage, whereas a cost-free scenario incorrectly predicted no trade-off.ConclusionsOur mechanistic model fitting to experimental data provides novel insights into the link between energy costs and reallocation due to induced resistance within-individual, and trade-offs among individuals of selected lines. These will be useful to better understand the exact role of energy allocation in the evolution of host defenses, and for predicting the emergence of trade-offs in genetic selection.

Two case reports of biliary stent infections by extensively drug-resistant Escherichia coli carrying blaNDM-5 at a tertiary-care hospital in West Bengal, India.

Rising antimicrobial resistance (AMR) is an acute public health emergency impeding the clinical efficacy of surgical interventions. Biliary stent placement is one of the routine surgical procedures that rarely lead to infections that are empirically managed by broad-spectrum β-lactams and fluoroquinolones. Critical priority pathogens, such as carbapenem-resistant Escherichia coli challenge treatment outcomes and infection prevention. Two carbapenem-resistant Escherichia coli isolates recovered from biliary stent-infected patients were investigated for drug resistance and molecular typing from a tertiary-care hospital in eastern India. The isolates were extensively drug-resistant (XDR) and remained susceptible to aminoglycosides, tigecycline, fosfomycin, or colistin. Carbapenemase blaNDM-5 was carried by both the isolates that either belonged to strain type ST361 or ST405. This is the first report of carbapenem-resistant Escherichia coli carrying blaNDM-5 being recovered from biliary stent infections in India. Targeted antibiotic therapy is pivotal for the XDR infections, while molecular typing facilitates infection prevention measures by source tracking and control.

Genetically attenuated parasites show promise as a next-generation malaria vaccine.

Metabolically active, genetically attenuated Plasmodium falciparum parasite lines are promising second-generation malaria vaccine candidates. Lamers et al. and Roozen et al. demonstrated in recent Phase 1/2a trials that GA2 parasites, designed to arrest late during liver-stage development and transmitted via mosquito bites, can induce substantial protection against sporozoite challenge infection.

Improving the odds of survival: transgenerational effects of infections.

Recent studies argue for a novel concept of the role of chromatin as a carrier of epigenetic memory through cellular and organismal generations, defining and coordinating gene activity states and physiological functions. Environmental insults, such as exposures to unhealthy diets, smoking, toxic compounds, and infections, can epigenetically reprogram germ-line cells and influence offspring phenotypes. This review focuses on intergenerational and transgenerational epigenetic inheritance in different plants, animal species and humans, presenting the up-to-date evidence and arguments for such effects in light of Darwinian and Lamarckian evolutionary theories. An overview of the epigenetic changes induced by infection or other immune challenges is presented, and how these changes, known as epimutations, contribute to shaping offspring phenotypes. The mechanisms that mediate the transmission of epigenetic alterations via the germline are also discussed. Understanding the relationship between environmental fluctuations, epigenetic changes, resistance, and susceptibility to diseases is critical for unraveling disease etiology and adaptive evolution.

Antibodies and Inflammation: Fecal Biomarkers of Gut Health in Domestic Ruminants.

Gastrointestinal infections present major challenges to ruminant livestock systems, and gut health is a key constraint on fitness, welfare, and productivity. Fecal biomarkers present opportunities to monitor animal health without using invasive methods, and with greater resolution compared to observational metrics. Here we developed enzyme-linked immunosorbent assays for three potential fecal biomarkers of gut health in domestic ruminants: two immunological (total immunoglobulin [Ig]A and total IgG) and one inflammatory (lactoferrin). We analytically validated the assays, then evaluated whether they could be used as a biomarker of clinically diagnosed gastrointestinal pathologies in cattle (Bos taurus), and finally comparedthem with helminth fecal egg counts in sheep (Ovis aries). The analytes were detected above the lower limits of detection in cattle, sheep, and goats. Fecal IgA and lactoferrin were higher in cattle with infectious pathologies (strongyles, coccidiosis and symptomatic Johne's disease) compared to healthy controls. Lactoferrin was additionally higher in animals with infectious pathologies compared to noninfectious pathologies, and to asymptomatic Johne's cases. No significant relationships were found with sheep fecal egg counts. These initial findings suggest that fecal IgA and lactoferrin may be useful biomarkers of poor gastrointestinal health in cattle, and that fecal lactoferrin is specific to active inflammation caused by infectious agents. These could be incorporated into the growing suite of noninvasive ecoimmunological tools and used to understand ruminant gut health in a range of species. Applications include improving treatment regimens for gastrointestinal infections, and understanding wildlife physiological responses to infectious challenges.

In vitro culture of the parasitic stage larvae of hematophagous parasitic nematode Haemonchus contortus.

Current research on common parasitic nematodes is limited because their infective stages cannot be propagated in vitro. Here, we report a culture system for developing L4s of Haemonchus contortus, a blood-feeding nematode of ruminants. Our results demonstrated that a proportionate mixture of NCTC-109 to Luria-Bertini (1:2) media promoted the formation of early L4s and then into late L4s upon inclusion of 12.5% (v/v) defibrinated blood, albeit with a decline in survival. Adding antioxidants (0.3 mg/mL of L-glutathione or 200 nmol of vitamin C) improved survival of L4s, with approximately 90% developing to late L4s by 22 days. These L4s showed parallel morphological features (such as digestive and reproduction systems) compared with in vivo L4s at day 7 (following challenge infection), although with delayed development. Our work optimized the in vitro culture system for L4s while providing an important platform for in-depth molecular research on Haemonchus and other related parasitic nematodes.

Staffing Paradigm for Infection Prevention and Control in the Era of Antimicrobial Resistance: the Veterans Health Administration Experience.

Antimicrobial resistance and other emerging healthcare complexities continue to challenge infection prevention and control (IPC) resources. The Veterans Health Administration developed a comprehensive prevention approach to address multidrug-resistant organisms (MDROs), including a unique staffing model to complement infection preventionists. In particular, the MDRO Prevention Coordinator was established to support MDRO prevention initiatives. Alternative staffing models, including to support pathogen-specific needs in an era of antimicrobial resistance, are vital for adaptable and sustainable IPC programs.

Management and Outcome of Invasive Clindamycin-Resistant MRSA Community-Associated Infections in Children.

Clindamycin resistance among community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) complicates the management of a challenging infection. Little data exist to guide clinicians in the management of invasive clindamycin-resistant CA-MRSA infections in children and studies using oral regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid for treatment of these infections are limited. We sought to reevaluate antibiotic management among invasive CA-MRSA at a tertiary children's hospital. Cases of invasive clindamycin-resistant MRSA infections in children were identified through an ongoing S. aureus surveillance study. Eligible cases were those occurring in otherwise healthy children from 2011-2021. Medical records were reviewed. Thirty-four subjects met inclusion criteria. The most common diagnoses were osteomyelitis (n = 17) and deep abscess (n = 7). The median duration of IV therapy was 11.5 days (IQR 6-42 days) and total therapy (IV + oral) was 32 days (IQR 23-42). Overall, 50% of patients were transitioned to oral therapy. Definitive antibiotics used for treatment included vancomycin (n = 15), TMP/SMX (n = 9), linezolid (n = 7), ceftaroline (n = 2), and doxycycline (n = 1). Cure rates were similar across definitive antibiotic therapies (vancomycin-73.3%; TMP/SMX-88.9%; ceftaroline 50%; linezolid and doxycycline-100%). Three subjects died of MRSA disease; two definitively treated with vancomycin and one with ceftaroline. Vancomycin is the most commonly used agent in the treatment of invasive clindamycin-resistant CA-MRSA in children at our center. However, TMP/SMX and linezolid can be considered as oral options when completing treatment in select cases. Further work is needed to evaluate the optimal management of these infections.

Virulent Bacteriophages for Controlling Shiga Toxin-Producing Escherichia coli (STEC) Without Inducing Toxin Production.

Shiga toxin-producing Escherichia coli (STEC) infections pose a significant public health challenge, characterized by severe complications including hemolytic uremic syndrome (HUS) due to Shiga toxin (Stx) production. Current therapeutic approaches encounter a critical limitation, as conventional antibiotic treatment is contraindicated due to its propensity to trigger bacterial SOS response and subsequently enhance Stx production, which increases the likelihood of developing HUS in antibiotic-treated patients. The lack of effective, safe therapeutic options has created an urgent need for alternative treatment strategies for STEC infections. This study investigates the therapeutic potential of virulent bacteriophages (phages) against STEC O157:H7. Our findings demonstrate that these phages effectively reduce STEC populations to levels comparable to ciprofloxacin treatment, while crucially avoiding the induction of SOS response and subsequent enhancement of Stx production. This is a significant advantage over conventional antibiotics which increase Stx levels. Furthermore, these phages exhibited broad-spectrum antimicrobial activity against multiple clinical STEC isolates without triggering toxin expression. The capability of virulent phages to effectively control STEC without enhancing toxin production represents a promising therapeutic strategy that combines antimicrobial efficacy with safety considerations. These characteristics indicate that virulent phages represent a potential solution to address the current therapeutic challenges in STEC infections, particularly in mitigating the risk of HUS development in infected patients.

Antimicrobial Activities of Citrus Seed and Leaf Extracts Against Selected Bacterial and Fungal Pathogens Linked to Human Diseases: In vitro Experimental Study in Musanze, Rwanda

Antimicrobial resistance has caused major challenges in both bacterial and fungal infections. Therefore, the current study was designed to evaluate the antimicrobial activity with different crude extracts of leaves and seeds of Citrus limon against Gram-positive (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa) and fungi (Cryptococcus neoformans and Candida albicans) obtained from different clinical settings. Filtrate extracts after maceration technique and the phytochemical substances detected in plants were flavonoid, saponin, alkaloid, glycoside, and resin under investigation. In vitro, a disc diffusion assay was applied to measure the inhibition zone of the plant effect in millimeters (mm). It was observed that Citrus limon activity showed the highest on ethanolic seed against Staphylococcus aureus and the lowest activity plant observed on methanolic leaf extract against Klebsiella oxytoca. The mean values of Citrus limon extract convinced there was no statistically significant correlation among extract solvents used in the study (ρ > 0.05). Oxacillin was used as the positive control and discs without antibiotic content as the negative control during testing. To conclude, ethanolic seed extract has shown the highest effect against Staphylococcus aureus and Salmonella typhi from isolate. Indeed, plant extracts that showed potential effectiveness, such as (Citrus leaves and seeds) can be used as natural alternative preventive measures to control pathogenic bacterial diseases and prevent the rise of antibiotic resistance. Furthermore, studies to evaluate the in vivo potential in an animal model are recommended. Keywords: Citrus limon, Crude extract, Bacteria, Fungi, Antimicrobial resistance.

Negative Swelling and Mechanical Self‐Enhancement TAFe@PVA Photothermal Hydrogel Mediated Via Semi‐Crystallization for Medical Implants

AbstractMedical implants, important consumables, significantly promote patients’ healthcare, but still face challenges of foreign body responses and bacterial infection. Hydrogels can be ideal alternative materials, however, a few of them can meet the requirements. Herein, a TAFe@PVA photothermal hydrogel integrating with negative swelling, long‐term stability, antibacterial, anti‐adhesion, and tissue mechanical matching is developed to solve these issues. The TAFe@PVA hydrogel is crosslinked by H‐bonds and microcrystal domains which both can be enhanced by cations or anions based on Hofmeister effect, showing unique negative swelling and long‐term mechanical self‐enhancement performances in the physiological fluid. Attributing to self‐polymerization of tannic acid (TA) and negative swelling of polyvinyl alcohol (PVA) molecular networks, TAFe complexes can be strongly locked in PVA molecular networks, reaching long‐term photothermal stability. The TAFe@PVA hydrogel also exhibits great biocompatibility, anti‐oxidation, anti‐adhesion, and anti‐bacterial performances, comparing to the traditional implant material. Since the TAFe@PVA hydrogel can better match with skin tissues, fewer macrophages and myofibroblasts are activated, which depresses unexpected foreign body responses. Finally, the TAFe@PVA hydrogel as the implant can effectively solve abdominal adhesions after abdominal operation and promote defects healing. This study introduces a promising hydrogel implant, which potentially extends hydrogels to wider medical applications.

Life‐history trade‐offs and stress resistance in Drosophila melanogaster populations adapted to pathogenic bacterial infection

AbstractEvolution of increased immune defence is often limited by costs: correlated changes in other traits (viz. life‐history traits) that otherwise reduce the fitness of the host organisms. Experimental evolution studies are useful for understanding the evolution of immune function and correlated changes in other traits. We experimentally evolved replicate Drosophila melanogaster populations to better survive infection challenges with an entomopathogenic bacteria, Enterococcus faecalis. Within 35 generations of directional selection, selected populations showed a marked increase in post‐infection survival than ancestrally paired controls. We next measured various life‐history traits of these populations. Our results show that the selected populations do not differ from control populations for larval development time and body weight at eclosion. No difference is also observed in case of fecundity and longevity (following the acute phase of infection), either when the flies were subjected to infection or when the flies were uninfected, although infected flies from all populations die much earlier than uninfected flies. Selected populations are either equally good or occasionally better as the control populations at surviving abiotic stressors (starvation and desiccation), although infected flies from all populations are more susceptible to stress than uninfected flies. Therefore, we conclude that (a) D. melanogaster populations can rapidly evolve to be more immune to infection with E. faecalis, (b) the evolution of increased defence against E. faecalis entails no life‐history cost for the hosts and (c) evolving defence against a biotic threat (pathogen) does not make flies more susceptible to abiotic stressors.

Protection Conferred by Gallid Alphaherpesvirus 2 Vaccines Against Immunosuppression Induced by Very Virulent Plus (vv+) Marek's Disease Virus Strains in Commercial Meat Type Chickens.

Very virulent plus Marek's disease virus (vv+MDV) induces severe immunosuppression in commercial chickens. In this study, we evaluated how three Gallid alphaherpesvirus 2 (GaHV-2) vaccines (CVI-988, rMd5-BAC∆Meq, and CVI-LTR) protected against two negative outcomes of vv+MDV infection: (1) reduced viability and frequency of immune cells in the spleen and (2) decreased efficacy of the CEO (chicken embryo origin) vaccine against infectious laryngotracheitis challenge. At 25 days post-infection with vv+MDV 686, all vaccines are protected against the reduced viability of splenocytes. However, there were differences in the frequency of splenic immunophenotypes among groups. Compared to the uninfected control, the frequency of B cells was reduced in the CVI-988/686 group but not in the rMd5-BAC∆Meq/686 and CVI-LTR/686 groups. T cell subset frequencies showed no difference between the negative controls and CVI-988/686; however, there was a reduction in activated CD4+ T cells in the rMd5-BAC∆Meq/686 group and in activated CD4+, activated CD8+, and γδ+ T cells in the CVI-LTR/686 group. We also demonstrated that the three vaccines protected against MDV-induced tumors, but only rMd5-BAC∆Meq and CVI-LTR protected against the negative impact of vv+MDV 648A strain on CEO vaccine efficacy. Our findings demonstrate important differences in the biology and/or mechanisms of protection of these vaccines.