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23 pages, 2269 KB  
Article
Cu-Nanoparticle-Doped Amino-MIL-101(Fe)-Functionalized Graphene Oxide Nanocomposite: Synthesis, Characterization, Performance Evaluation and Environmental Applications for Enhanced Tetracycline Antibiotic Removal
by Doaa S. Al-Raimi, Faten M. Ali Zainy and Amr A. Yakout
Nanomaterials 2026, 16(9), 551; https://doi.org/10.3390/nano16090551 (registering DOI) - 30 Apr 2026
Abstract
Tetracycline antibiotics are increasingly detected in aquatic environments because of their ecological risks and persistence, while conventional wastewater treatment processes are often insufficient for their effective removal from water. Here, we introduce a novel 3D graphene oxide-based nanocomposite that stacks Cu-NPs and amino-functionalized [...] Read more.
Tetracycline antibiotics are increasingly detected in aquatic environments because of their ecological risks and persistence, while conventional wastewater treatment processes are often insufficient for their effective removal from water. Here, we introduce a novel 3D graphene oxide-based nanocomposite that stacks Cu-NPs and amino-functionalized MIL-101(Fe) (denoted by Cu/NH2-MIL-101(Fe)@GO) to effectively remove tetracycline (TC) and oxytetracycline (OTC) from environmental water samples. XPS, XRD, TEM, SEM, and FTIR analyses were conducted to characterize the structure and surface morphology of the Cu/NH2-MIL-101(Fe)@GO nanocomposite. Overall, it was confirmed that GO, NH2-MIL-101(Fe), and Cu-NPs were successfully incorporated, resulting in a porous material with high access to Cu-related sites as well as oxygen- and nitrogen-based functionalities (such as amino-, hydroxy-, and carboxy-groups). This hybrid system facilitates the adsorption by complementary mechanisms like surface complexation/chelation at Cu and Fe centers with the pH-dependent tetracycline species in electrostatic interactions, hydrogen bonding, π–π stacking, and molecule confinement in the metal–organic framework (MOF) pores, and by the synergistic effects at the GO–MOF(Fe)–Cu junction interfaces. The batch adsorption studies showed that the quick and efficient uptake of the two antibiotics at pH 6.5, with removal rates of 99.65–99.83%, was achieved by 15.0 mg of Cu/NH2-MIL-101(Fe)@GO at an initial concentration of 20 ppm in 40 min at 25 °C. Equilibrium data were found to be well-fitted by the Langmuir isotherm (R2 = 0.908–0.909), suggesting monolayer-dominated adsorption with the maximum capacity of 769.8–775.2 mg g−1. The adsorption kinetics was well-described by the pseudo-second order model (R2 = 0.9641–0.9749), which agreed with the strong binding between the tetracyclines and active sites of the nanocomposite. The main novelty of this work consists of the design of a single recoverable platform integrating GO-based preconcentration, pore accessibility of NH2-MIL-101(Fe), and Cu-driven complexation, which led to the strong removal of tetracyclines under a relevant range of water conditions. These findings demonstrate that Cu/NH2-MIL-101(Fe)@GO could serve as a promising high-efficiency and potentially reusable adsorbent for removing tetracycline from aqueous solution, which provides a more sustainable approach for pharmaceutical wastewater treatment. Full article
(This article belongs to the Topic Functionalized Materials for Environmental Applications)
17 pages, 324 KB  
Review
Does Probiotic Intake Enhance the Efficacy of Oral Fungal Infection Treatment?
by Sebastian Kłosek, Michalina Szymczak-Paluch, Aleksandra Bernaś and Sebastian Gawlak-Socka
Nutrients 2026, 18(9), 1433; https://doi.org/10.3390/nu18091433 (registering DOI) - 30 Apr 2026
Abstract
Oral candidiasis (OC) is the most frequent fungal infection among users of dental prosthetic devices, immunocompromised patients, and those who underwent chemotherapy treatment and had a complication of long-term antibiotic therapy. About 150 species of Candida fungi have been described, whereas over 80% [...] Read more.
Oral candidiasis (OC) is the most frequent fungal infection among users of dental prosthetic devices, immunocompromised patients, and those who underwent chemotherapy treatment and had a complication of long-term antibiotic therapy. About 150 species of Candida fungi have been described, whereas over 80% of oral fungal infections are attributed to the opportunistic pathogen Candida albicans. Pain, dryness of oral mucosa, pathological lesions, and intermittent mucosal bleeding are the main symptoms that worsen the daily functioning of the abovementioned fungal-infected patients. A promising adjunctive strategy may involve the use of probiotic bacteria to attenuate fungal colonization in the oral cavity in order to reduce the need for conventional treatment, which carries a risk of antifungal drug resistance—a significant problem worldwide. Probiotic formulations mostly incorporate commensal bacteria that naturally inhabit oral ecosystems such as Lactobacillus spp., Bifidobacterium spp., Bacillus spp., and others. Probiotic organisms may contribute to the restoration of oral microbiome homeostasis through numerous mechanisms, such as competitive control of Candida species numbers, better adhesion to oral mucosa and production of bioactive compounds and antimicrobial metabolites. Despite many studies, the current evidence base remains heterogeneous. Well-designed studies across diverse populations are required to determine whether probiotic-based interventions can be an effective and clinically useful alternative or adjunct to standard antifungal therapy of OC. Full article
(This article belongs to the Section Nutrition Methodology & Assessment)
14 pages, 765 KB  
Article
Isolation, Identification, and Drug Susceptibility Testing of the Pathogen Causing Perforation Disease in Giant Spiny Frog Tadpoles (Quasipaa spinosa)
by Qinglian Wu, Xiandong Xu, Jianqin Li, Han Qiu, Huanhuan Huo, Mo Peng, Chungen Wen and Gang Yang
Microorganisms 2026, 14(5), 1016; https://doi.org/10.3390/microorganisms14051016 - 30 Apr 2026
Abstract
A pathogenic bacterium strain, LBK2, was isolated from giant spiny frog (Quasipaa spinosa) tadpoles infected with perforation disease in this study. Pathogenic strain LBK2, a Gram-negative bacterium with a certain degree of infectivity, was demonstrated to cause anorexia, lethargy, epidermal necrosis, [...] Read more.
A pathogenic bacterium strain, LBK2, was isolated from giant spiny frog (Quasipaa spinosa) tadpoles infected with perforation disease in this study. Pathogenic strain LBK2, a Gram-negative bacterium with a certain degree of infectivity, was demonstrated to cause anorexia, lethargy, epidermal necrosis, and abdominal perforation in tadpoles in artificial infection experiments. The identification results of 16S rDNA gene sequencing showed that pathogenic strain LBK2 was identified as Pseudomonas sp. Virulence gene identification displayed that strain LBK2 carried three virulence genes: aer, epr, and fla. Finally, the antibiotic susceptibility testing of 11 antibiotics suggested that strain LBK2 was highly sensitive to nine antibiotics, including chloramphenicol, enrofloxacin, and rifampicin, but was resistant to erythromycin, sulfamethoxazole/trimethoprim, and low-concentration trichloroisocyanuric acid. This study determined the pathogenicity of Pseudomonas sp. to giant spiny frog tadpoles based on histopathological analysis and virulence factor carriage, and the drug susceptibility testing further provided a scientific basis for the selection of drugs in the prevention and treatment of abdominal perforation disease in giant spiny frog tadpoles. Full article
(This article belongs to the Special Issue Pathogens in Aquaculture Environments)
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18 pages, 2533 KB  
Article
Oxytetracycline Removal in a PLA-Immobilized Laccase Bioreactor: Experimental Evaluation and Diffusion–Convection–Reaction Modeling
by Paula Garín, Humberto Brito, Isabel Cáceres and Carola Bahamondes
Catalysts 2026, 16(5), 398; https://doi.org/10.3390/catal16050398 - 30 Apr 2026
Abstract
This work presents a novel integrative approach to the design and computational modeling of a bioreactor system for the enzymatic removal of antibiotics from aquatic environments. The study focuses on a three-dimensional mathematical model developed to resolve the diffusion–convection–reaction dynamics within the system. [...] Read more.
This work presents a novel integrative approach to the design and computational modeling of a bioreactor system for the enzymatic removal of antibiotics from aquatic environments. The study focuses on a three-dimensional mathematical model developed to resolve the diffusion–convection–reaction dynamics within the system. Programmed in MATLAB R2025a, the model integrates theoretical equations to determine the diffusion and convection coefficients, while the reaction rate constant was precisely determined through the experimental degradation data of oxytetracycline. To support this modeling, laccase was covalently immobilized on a chemically modified polylactic acid (PLA) matrix, achieving a 95.6% immobilization yield. Simulation results revealed that the system is primarily governed by the convection constant and that degradation efficiency is significantly optimized by reducing the reactor’s internal diameter. These findings demonstrate that the coupling of theoretical transport phenomena with experimentally derived kinetics provides a high-resolution tool for predicting bioreactor performance. By combining biocatalysis, materials science, and computational modeling, this research offers a scalable and environmentally friendly solution with direct implications for the development of advanced water treatment technologies. Full article
(This article belongs to the Special Issue Enzyme Design, Engineering and Applications in Efficient Biocatalysis)
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18 pages, 529 KB  
Review
Micro/Nanoplastics and Periodontitis: An Environmental Microbiology Perspective on Oral Retention and Systemic Risk
by Mark Cannon, John Peldyak and Paul Reynolds
Microorganisms 2026, 14(5), 1014; https://doi.org/10.3390/microorganisms14051014 - 30 Apr 2026
Abstract
Micro- and nanoplastics (MNPs) have now been detected in human blood, placenta, and arterial tissue, yet the oral cavity has received strikingly little mechanistic attention despite serving as a primary portal of environmental exposure and a local site of polymer generation from dental [...] Read more.
Micro- and nanoplastics (MNPs) have now been detected in human blood, placenta, and arterial tissue, yet the oral cavity has received strikingly little mechanistic attention despite serving as a primary portal of environmental exposure and a local site of polymer generation from dental and oral-care materials. This narrative review addresses that gap from an environmental microbiology perspective, synthesizing recent literature on periodontal disease, chronic low-grade inflammation, oral biofilms, dental materials, microbial–plastic interactions, and systemic chronic disease risk. Unlike prior reviews, we apply an explicit three-tier evidentiary framework (established, plausible, unproven) that distinguishes what is directly demonstrated from what is biologically plausible but unproven, and we situate the periodontal environment specifically as a particle-retention and inflammatory-amplification niche. The strongest direct oral evidence shows that human dental calculus harbors at least 26 microplastic types, dominated by polyamide (41.4%), polyethylene (32.7%), and polyurethane (7.0%). Polyethylene isolated from calculus induces cytotoxicity, apoptosis, impaired migration, NF-κB activation, and upregulation of IL-1β and IL-6 in human gingival fibroblasts. From a microbiological standpoint, oral organisms actively degrade methacrylate dental polymers, and the degradation products of these polymers reciprocally modulate oral bacterial virulence gene expression. Across experimental systems, MNPs activate oxidative stress, inflammasome signaling, macrophage polarization, and barrier dysfunction, pathways that overlap extensively with periodontal pathobiology. Adjacent environmental microbiology demonstrates that plastic-associated biofilms enhance extracellular polymeric substance production, quorum sensing, pathogen persistence, and antibiotic resistance gene transfer, supporting a plausible but not yet validated oral plastisphere within plaque and calculus. We argue that periodontitis should be reconceptualized as a chronically inflamed particle-processing interface that may increase local MNP retention, cellular reactivity, and systemic inflammatory spillover, with implications for cardiovascular, metabolic, and other chronic disease risk pathways. Current evidence does not yet prove that environmental MNP exposure causes human periodontitis, and that evidentiary boundary is maintained throughout. A priority research agenda is proposed, centered on contamination-controlled subgingival biomonitoring stratified by periodontal status, spatially resolved multi-species biofilm models, polymer source attribution, and longitudinal clinical studies linking oral plastic burden to inflammatory and systemic outcomes. Full article
(This article belongs to the Special Issue Oral Diseases and Microbiome)
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19 pages, 3739 KB  
Article
Bacillus velezensis M4 from Northeast Chinese Soybean Paste Combines Nattokinase and Antibacterial Activities
by Yin Feng, Yuexin Gao, Linxi Wang, Bo Nan, Jingsheng Liu and Yuhua Wang
Foods 2026, 15(9), 1553; https://doi.org/10.3390/foods15091553 - 30 Apr 2026
Abstract
A bacterial strain M4 exhibiting high nattokinase (NK) activity and favorable antibacterial properties was isolated from fermented soybean paste in Northeast China. Based on morphological observation, physiological and biochemical characterization, 16S rDNA sequence analysis, and whole-genome sequencing, the strain was identified as Bacillus [...] Read more.
A bacterial strain M4 exhibiting high nattokinase (NK) activity and favorable antibacterial properties was isolated from fermented soybean paste in Northeast China. Based on morphological observation, physiological and biochemical characterization, 16S rDNA sequence analysis, and whole-genome sequencing, the strain was identified as Bacillus velezensis. Its probiotic potential and safety were systematically evaluated using a combination of in vitro assays and genome mining. Genomic analysis revealed that M4 possessed a complete genome consisting of a single circular chromosome of 4,473,838 bp with a GC content of 46.94%, encoding 4516 predicted proteins. Functional domain annotation identified four proteins (XLQ58132.1, XLQ58158.1, XLQ59409.1, and XLQ59873.1) containing both the Peptidase inhibitor I9 and Peptidase S8 domains, confirming the presence of the typical molecular signature of NK. Furthermore, the genome harbored 132 genes encoding carbohydrate-active enzymes, 37 biosynthetic gene clusters, and 142 genes encoding proteolytic enzymes. Comparative genomic analysis revealed a close phylogenetic relationship with other B. velezensis strains and identified 98 strain-specific genes. Safety assessment demonstrated that M4 exhibited no hemolytic activity, was susceptible to eight commonly tested antibiotics, and lacked genes encoding high-risk virulence factors. Probiotic characterization indicated that M4 exhibited certain levels of gastrointestinal tolerance, acid resistance, bile salt resistance, antioxidant activity, and antibacterial properties. In conclusion, B. velezensis M4 shows potential for development as a functional strain. Full article
(This article belongs to the Section Food Microbiology)
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12 pages, 427 KB  
Article
Association Between Abscess Size, Inflammatory Markers, and the Need for Drainage in Renal Abscesses
by Dragoș Puia, Marius Ivănuță, Ovidiu Daniel Bîcă, Nicolae Stoican, Mihaela Corlade-Andrei, Bogdan Doroftei and Cătălin Pricop
Diseases 2026, 14(5), 160; https://doi.org/10.3390/diseases14050160 - 30 Apr 2026
Abstract
Background: Renal abscesses represent a serious complication of urinary tract infections, with management decisions often being guided by abscess size and clinical parameters. However, there is no universally accepted size threshold for intervention, and the role of inflammatory markers such as white blood [...] Read more.
Background: Renal abscesses represent a serious complication of urinary tract infections, with management decisions often being guided by abscess size and clinical parameters. However, there is no universally accepted size threshold for intervention, and the role of inflammatory markers such as white blood cell count (WBC) and C-reactive protein (CRP) in guiding treatment remains uncertain. We aimed to evaluate the relationship between abscess size, inflammatory markers, and the need for drainage in patients with renal abscesses treated in a tertiary urology clinic. Methods: A retrospective analysis was conducted on 103 adult patients diagnosed with renal abscesses between 2020 and 2025. Patients were categorized into two groups based on abscess size: Group A (<50 mm) and Group B (50 mm). Results: The cohort included 59 females and 44 males, with a mean age of 60.5 years. Computed tomography was used for diagnosis in 55.3% of cases. The most common comorbidities were hypertension (46.6%) and diabetes mellitus (40.8%). Microbiological cultures most frequently identified Escherichia coli (38.3%) and Klebsiella spp. (21.7%). Antibiotic resistance was highest to ampicillin (79.5%), while amikacin (5.8%) and piperacillin/tazobactam (6.2%) showed the lowest resistance rates. Conservative antibiotic therapy was effective in 43 patients (42.7%), whereas 60 patients (58.3%) required percutaneous drainage. Abscess size was associated with invasive intervention, with 88.1% of drained abscesses measuring ≥50 mm compared to 9.1% in the conservatively managed group (p < 0.001). Patients with larger abscesses had significantly lower haemoglobin levels (p = 0.003), while no significant differences were observed in WBC or CRP levels. Conclusions: Abscess size was associated with the need for drainage, supporting its role in clinical decision-making. In contrast, inflammatory markers such as WBC and CRP showed limited value in predicting the need for intervention in this cohort. These findings should be interpreted in the context of the retrospective design. Full article
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14 pages, 12568 KB  
Article
Management of Complex Peri-Prosthetic Joint Infection Following Total Knee Arthroplasty with Soft Tissue Defects: Case Series and Multidisciplinary Approach
by Katelynn Murray Whelan, Gerard Anthony Sheridan, Kenneth Joyce, Alan Hussey, Jason Hoellwarth and Justina Baltrunaite
J. Pers. Med. 2026, 16(5), 238; https://doi.org/10.3390/jpm16050238 - 30 Apr 2026
Abstract
Background: Peri-prosthetic joint infection (PJI) following total knee arthroplasty complicated by soft tissue compromise presents a major reconstructive challenge. Successful management requires the eradication of infection while restoring durable soft tissue coverage and limb function. This study reports the outcomes of a patient-specific, [...] Read more.
Background: Peri-prosthetic joint infection (PJI) following total knee arthroplasty complicated by soft tissue compromise presents a major reconstructive challenge. Successful management requires the eradication of infection while restoring durable soft tissue coverage and limb function. This study reports the outcomes of a patient-specific, multidisciplinary orthoplastic approach to complex knee PJI. Methods: We retrospectively reviewed five patients with complex infected knee arthroplasty and associated soft tissue compromise managed at our institution between 2021 and 2025 by a single orthopaedic surgeon and two plastic reconstructive surgeons. All cases required personalized management, including the use of custom spacers, patient-specific orthopaedic reconstruction, and individualized soft tissue reconstruction techniques. Data collected included patient demographics, infection characteristics, reconstructive techniques, and functional outcomes. Results: All patients achieved durable soft tissue coverage and infection eradication at final follow-up. Of the five patients, one underwent primary closure of a persistent sinus, one required a local axial bi-pedicled flap for sinus control and soft tissue closure, two were managed with medial gastrocnemius flaps, and one complex case with an associated bone defect required a custom-designed spacer to achieve stability and dead-space management. Conclusions: In this retrospective case series, we aim to demonstrate that complex knee PJI with associated soft tissue defects may be successfully managed with an individualized, multidisciplinary strategy. We aim to demonstrate the feasibility of such an approach in a tertiary referral centre and to highlight the importance of customisation in achieving infection control and limb preservation. Full article
(This article belongs to the Special Issue Orthopedic Diseases: Advances in Limb Reconstruction)
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12 pages, 773 KB  
Perspective
Repurposing Non-Infectious Therapeutic Agents to Aid in the Treatment of Chronic Biofilm Infections
by Lila Berle, Yash Sodhi, Poonam Mathur, Nazary Nebeluk and James B. Doub
Med. Sci. 2026, 14(2), 226; https://doi.org/10.3390/medsci14020226 - 30 Apr 2026
Abstract
Antibiotics primarily exert their effect on planktonic microbial states, limiting their ability to eradicate biofilms commonly seen in chronic infections. This is because the minimal inhibitory concentration of antibiotics needed to kill microbes in biofilms can be up to 1000 times greater than [...] Read more.
Antibiotics primarily exert their effect on planktonic microbial states, limiting their ability to eradicate biofilms commonly seen in chronic infections. This is because the minimal inhibitory concentration of antibiotics needed to kill microbes in biofilms can be up to 1000 times greater than when microbes are in their planktonic state. Yet up to 70% of all chronic infections are associated with a biofilm component. Consequently, novel therapeutics are needed to aid in the treatment of chronic biofilm infections. One such approach is to repurpose drugs that have demonstrated safety for non-infectious clinical indications. The main advantage of this approach is that the agents have already been shown to be safe for human administration, which can expedite clinical trial development of agents for biofilm infections. Unfortunately, most clinicians are unaware of the antimicrobial properties of some commonly used drugs. Thus, the aim of this Perspective was to discuss the potential of four drugs that have theoretical promise as adjuvants in the treatment of chronic biofilm infections. This was accomplished by providing detailed discussion of each agent with respect to current clinical use, potential mechanisms of antimicrobial activity, and present data to support use as adjuvant biofilm agents. Full article
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17 pages, 9499 KB  
Article
Genome-Based Analysis of Chromosomal Colistin Non-Susceptibility in Stenotrophomonas pavanii Isolated from the Phycosphere of Pectinodesmus pectinatus
by Heejin Ahn, Hyunwoo Zin, Muhammad Akmal and Tae-Jin Choi
Antibiotics 2026, 15(5), 451; https://doi.org/10.3390/antibiotics15050451 - 30 Apr 2026
Abstract
Background/Objectives: Freshwater microalgae–bacteria consortia are increasingly utilized in wastewater treatment and biomass production. However, bacteria associated with the algal phycosphere may act as environmental reservoirs of multidrug-resistant (MDR) phenotypes and antibiotic resistance genes (ARGs), including resistance to last-resort antibiotics such as colistin. Methods: [...] Read more.
Background/Objectives: Freshwater microalgae–bacteria consortia are increasingly utilized in wastewater treatment and biomass production. However, bacteria associated with the algal phycosphere may act as environmental reservoirs of multidrug-resistant (MDR) phenotypes and antibiotic resistance genes (ARGs), including resistance to last-resort antibiotics such as colistin. Methods: An axenic culture of the freshwater microalga Pectinodesmus pectinatus was established using a NaClO-based cleaning protocol. Three phycosphere-associated bacterial strains (Chryseobacterium sp., Pseudomonas monteilii, and Stenotrophomonas pavanii) were isolated and identified by 16S rRNA gene analysis. Antimicrobial susceptibility testing was performed using broth microdilution against 16 antibiotics. Whole-genome sequencing of the most resistant isolate, S. pavanii, was conducted using Oxford Nanopore technology, followed by genome annotation and in silico resistome analysis using CARD, AMRFinderPlus, and ResFinder. Results: Among the three isolates, S. pavanii exhibited the broadest resistance profile, including high minimum inhibitory concentrations (MICs) to multiple β-lactams and colistin (MIC ≥ 16 μg/mL). No plasmid-borne mcr genes were detected. Instead, the genome encoded multiple chromosomal determinants potentially associated with polymyxin non-susceptibility, including lipid A and lipopolysaccharide modification pathways (e.g., arn genes and eptA), outer-membrane maintenance and LPS transport systems, multidrug efflux pumps, and regulatory elements. Integration of genomic and phenotypic data suggested that the observed colistin non-susceptibility may be associated with intrinsic chromosomal determinants inferred from whole-genome analysis. Conclusions: This study demonstrates that the P. pectinatus phycosphere can harbor multidrug-resistant (MDR) bacteria, including strains exhibiting colistin non-susceptibility potentially associated with a repertoire of intrinsic chromosomal resistance mechanisms inferred from genomic analysis. Therefore, freshwater microalgae-based systems should be considered potential environmental reservoirs contributing to the dissemination of antimicrobial resistance. Full article
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8 pages, 674 KB  
Article
Plasma and Intracellular Concentrations of Doxycycline and Azithromycin in Patients with Severe Scrub Typhus
by Debasree Kundu, Merylin Sebastian, Shadab Ahmad, Sohail Khan, Divya Dayanand, Blessed Winston Aruldhas, Binu Susan Mathew, Karthik Gunasekaran, Nalini Newbigging, Kundavaram P. P. Abhilash, Anand Zachariah, Ramya Iyadurai, Samuel George Hansdak, Sowmya Sathyendra, Thambu David Sudarsanam, Abi Manesh, John Victor Peter, Jeanne Salje, Ooriapadickal C. Abraham, Nicholas P. J. Day, Joel Tarning and George M. Vargheseadd Show full author list remove Hide full author list
Antibiotics 2026, 15(5), 450; https://doi.org/10.3390/antibiotics15050450 - 30 Apr 2026
Abstract
Background/Objectives: Scrub typhus, a life-threatening infection caused by Orientia tsutsugamushi, is treated with doxycycline or azithromycin. In severe disease, combination therapy with azithromycin and doxycycline had better clinical outcomes than either drug alone. However, it is not clear what causes the improved [...] Read more.
Background/Objectives: Scrub typhus, a life-threatening infection caused by Orientia tsutsugamushi, is treated with doxycycline or azithromycin. In severe disease, combination therapy with azithromycin and doxycycline had better clinical outcomes than either drug alone. However, it is not clear what causes the improved efficacy. To understand the same, we examined the plasma concentrations, intracellular concentrations, and efficacy of doxycycline, azithromycin, and both drugs in combination in 51 patients with severe scrub typhus. Methods: A randomly selected subset of adult (>18 years) participants from the INTREST trial (Clinical Trials Registry–India, number CTRI/2018/08/015159), who had been randomized in a 1:1:1 ratio to receive doxycycline, azithromycin, or both drugs, respectively, were included in this study for comparative drug concentration analysis. Blood samples were collected on days 0, 1, 3, and 7 to monitor bacterial load using quantitative polymerase chain reaction (PCR). Five milliliters of sterile blood were collected 3–10 h after the final dose on day 7 for comparative drug concentration measured using high-resolution multiple reaction monitoring. Data were analyzed in GraphPad Prism v.10.0.3. Results: Fifty-one patients (males, 59%; median age, 52 years) were enrolled. Fifteen, seventeen, and nineteen patients received azithromycin, doxycycline, and both, respectively. Doxycycline achieved a median plasma concentration of 1112 (42.51–5697) ng/mL and was undetectable intracellularly. The intracellular concentration of azithromycin (1127 [16.78–19,250] ng/mL) surpassed its plasma concentration (227.1 [48.78–1022] ng/mL). On day 3, PCR negativity rates were 56.24%, 93.3%, and 94.7% in the doxycycline, azithromycin, and combination groups, respectively. Conclusions: The high plasma concentrations of doxycycline and intracellular accumulation of azithromycin may contribute to improved clinical outcomes when used in combination. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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16 pages, 1373 KB  
Review
The Battle Against Pertussis: Discovery of Endogenous Human Proteins and Peptides as Toxin-Inhibitors
by Stefanie Lietz and Holger Barth
Toxins 2026, 18(5), 208; https://doi.org/10.3390/toxins18050208 - 29 Apr 2026
Abstract
The life-threatening disease pertussis, also known as whooping cough, is caused by a complex interplay of several virulence factors produced by the bacterium Bordetella (B.) pertussis. These include the AB-type protein toxin pertussis toxin (PT), the main causative agent of [...] Read more.
The life-threatening disease pertussis, also known as whooping cough, is caused by a complex interplay of several virulence factors produced by the bacterium Bordetella (B.) pertussis. These include the AB-type protein toxin pertussis toxin (PT), the main causative agent of pertussis. After infection with B. pertussis, PT is released and binds to its human target cells, which internalize PT. The enzyme subunit of PT is then taken up into the cytosol, where it catalyzes the ADP-ribosylation of the α-subunit of inhibitory GTP-binding proteins from the Gαi type. This ultimately leads to the development of the characteristic clinical symptoms associated with pertussis. Pertussis is a vaccine-preventable but highly infectious respiratory disease, and especially younger children are prone to develop severe pertussis. Despite the vaccination, over the past few years, increasing case numbers have been reported globally. Moreover, treatment options are strongly limited to antibiotics and symptomatic treatment. Therefore, novel therapies against toxin-mediated diseases are urgently required, while AB-type toxins such as PT are promising pharmacological targets to combat these associated diseases. To identify novel pharmacological inhibitors for AB-type toxins, huge potential lies within the human proteome/peptidome. Endogenous protein or peptide inhibitors for bacterial toxins might have evolved as part of the innate immunity and are awaited to be discovered. The scientific community is committed to identify potential candidates through targeted screening or explorative hypothesis-driven approaches. This review summarizes the recent efforts in the identification and characterization of the human body’s own proteins and peptides that inhibit PT. PT-inhibiting peptides were found by unbiased screening of peptide libraries from human hemofiltrate or hypothesis-driven evaluation, and PT-neutralizing mechanisms were discovered in cell-based approaches. The identification of endogenous peptides and proteins, e.g., defensins and α1-antitrypsin, as potent inhibitors of PT paves the way towards the development of novel therapeutic options against pertussis. Full article
(This article belongs to the Special Issue Bacterial Toxins and Immune System)
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21 pages, 1843 KB  
Article
Genomic Insights into the Probiotic Potential of Lactic Acid Bacteria Isolated from Tocosh: Traditional Peruvian Fermented Potatoes
by Vilma Julia Reyes, Marcial Silva-Jaimes, Liz Erika Cruz-Pio, Michel Abanto, Mario Taira and Pablo Ramirez
Int. J. Mol. Sci. 2026, 27(9), 3981; https://doi.org/10.3390/ijms27093981 - 29 Apr 2026
Abstract
Tocosh, an ancestral fermented potato product, relies on spontaneous processes near freshwater springs under extreme high-altitude conditions and represents an underexplored reservoir of microbial diversity with significant potential for the discovery of probiotics. This study provides, for the first time, a comprehensive probiogenomic [...] Read more.
Tocosh, an ancestral fermented potato product, relies on spontaneous processes near freshwater springs under extreme high-altitude conditions and represents an underexplored reservoir of microbial diversity with significant potential for the discovery of probiotics. This study provides, for the first time, a comprehensive probiogenomic characterization of 19 lactic acid bacteria (LAB) isolated from tocosh, in the Peruvian Andes, at three distinct altitudes—2992, 3882, and 4451 m above sea level (m.a.s.l.)—using whole genome sequencing (WGS) and bioinformatic profiling. A total of six species were identified: Lactiplantibacillus plantarum and Levilactobacillus brevis at all three study sites, Lacticaseibacillus paracasei and Lentilactobacillus buchneri at the lowest altitude (2992 m.a.s.l.), and Latilactobacillus curvatus and Latilactobacillus sakei at the highest altitudes (3882 and 4451 m.a.s.l.). Our results reveal that the extreme Andean environment is associated with stability in L. plantarum (genome sizes from 3.36 to 3.38 Mb) across all altitudinal levels. Functional analysis using CAZymes determined that L. brevis and L. buchneri act as primary degraders (high percentage of glycosyl hydrolases/carbohydrate binding) while L. curvatus and L. sakei function as primary builders through exopolysaccharide biosynthesis, likely a cryoprotective adaptation preventing cell damage during cold temperatures at high altitudes. Additionally, L. sakei and L. plantarum exhibited unique auxiliary activity (AA) enzymes, suggesting an oxidative mechanism to breach recalcitrant starch surfaces. All isolates were confirmed as genomically safe, lacking transferable antibiotic resistance genes and virulence factors. Pathogenic risk potential scores (PPRS) were consistently ≤ 2.0, fulfilling qualified presumption of safety (QPS) criteria. These findings provide the first genomic characterization of tocosh-associated LAB, establishing a basis for tocosh standardization, enabling the rational design of starter cultures that preserve ancestral traits and ensure microbiological safety in modern food applications. Full article
14 pages, 1778 KB  
Article
Molecular Epidemiology of the blaCTX-M Gene in Escherichia coli from a Pig Farm: Antimicrobial Resistance Profiles, Genetic Background, and Its Horizontal Transfer and Environmental Dissemination
by Ri-Han Jiang, Zi-Kui Liu, Bing Han, Dan-Ni Liao, Ji-Yun Li and Yong Wu
Microorganisms 2026, 14(5), 1007; https://doi.org/10.3390/microorganisms14051007 - 29 Apr 2026
Abstract
This study investigated the epidemiology, antimicrobial resistance, and transmission risks of β-lactamase, cefotaxime-hydrolyzing, Munich (blaCTX-M)-positive Escherichia coli (CTX-M-EC) in large-scale pig farms in Jiangxi Province (China). In total, 278 samples (manure, wastewater, drinking water, and flies) were collected. CTX-M-EC strains [...] Read more.
This study investigated the epidemiology, antimicrobial resistance, and transmission risks of β-lactamase, cefotaxime-hydrolyzing, Munich (blaCTX-M)-positive Escherichia coli (CTX-M-EC) in large-scale pig farms in Jiangxi Province (China). In total, 278 samples (manure, wastewater, drinking water, and flies) were collected. CTX-M-EC strains were isolated and analyzed using antimicrobial susceptibility testing, resistance gene profiling, multilocus sequence typing, and genetic environment analysis with gene transfer assessed by transduction experiments. Twenty-seven CTX-M-EC strains (9.71%) were isolated, all exhibiting multi-drug resistance with 100% resistance to cefotaxime, ciprofloxacin, and tetracycline, and >90% resistance to ceftazidime, florfenicol, and trimethoprim-sulfamethoxazole. Four blaCTX-M subtypes were identified. blaCTX-M-55 was the predominant subtype (70.37%) and was distributed across diverse sequence types and serotypes. Each strain harbored multiple antibiotic resistance genes, plasmids, and virulence genes. Mobile elements such as ISEcp1 and IS26 were detected surrounding the blaCTX-M gene, and 96.29% of strains successfully transferred the blaCTX-M gene via transduction. Clones highly homologous to pig manure strains were detected in flies and sewage, suggesting that this resistance gene can spread between animals, the environment, and vectors. These findings highlight the high transmission risk of blaCTX-M and underscore the need for rational antibiotic use, waste management, and vector control within a One Health framework. Full article
(This article belongs to the Special Issue Microbial Evolutionary Genomics and Bioinformatics)
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12 pages, 1173 KB  
Case Report
The Role of Genetic Testing in the Differential Diagnosis of Pustular Dermatoses: A Pediatric Case of Generalized Pustular Psoriasis Associated with the IL36RN Variant
by Maksymilian Markwitz, Paweł Głuszak, Anna Skorczyk-Werner, Natalia Welc, Aleksandra Dańczak-Pazdrowska, Aleksandra Wnuk-Kłosińska, Monika Bowszyc-Dmochowska, Marian Dmochowski, Anna Wiśniewska-Szymańska, Sandra Ważniewicz and Adriana Polańska
J. Clin. Med. 2026, 15(9), 3413; https://doi.org/10.3390/jcm15093413 - 29 Apr 2026
Abstract
General pustular psoriasis (GPP) is a rare, potentially life-threatening neutrophilic dermatosis. Pediatric cases are uncommon and often misdiagnosed due to overlapping clinical and histopathological features with other pustular dermatoses. We present a case of an 11-year-old boy, initially diagnosed with Sneddon–Wilkinson syndrome, who [...] Read more.
General pustular psoriasis (GPP) is a rare, potentially life-threatening neutrophilic dermatosis. Pediatric cases are uncommon and often misdiagnosed due to overlapping clinical and histopathological features with other pustular dermatoses. We present a case of an 11-year-old boy, initially diagnosed with Sneddon–Wilkinson syndrome, who presented with disseminated pustular eruptions, with no response to antibiotics, dapsone, and glucocorticosteroids. In histopathology, we observed subcorneal neutrophilic pustules. Due to atypical features and poor treatment response, the patient underwent genetic testing, which revealed a homozygous IL36RN gene c.338C>T (p.Ser113Leu) pathogenic variant, which enabled a definitive diagnosis of GPP. Treatment with acitretin led to clinical improvement. Pediatric GPP poses diagnostic and treatment challenges. Genetic testing for IL36RN pathogenic variants may aid in the diagnosis, especially in atypical cases. The presence of the biallelic IL36RN pathogenic variant supports the diagnosis of DITRA (Deficiency of the IL-36 Receptor Antagonist, ORPHA:404546)—a monogenic autoinflammatory form of GPP. Full article
(This article belongs to the Section Dermatology)
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