Trichosporon species are emerging opportunistic fungal pathogens associated with nosocomial infections, particularly in immunocompromised individuals. Accurate species identification and antifungal susceptibility testing are essential for appropriate clinical management. However, data on the distribution of Trichosporon species, the identification accuracy of matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF MS), and local epidemiological patterns in Hefei, China, remain limited. Demographic and clinical data from 99 patients corresponding to 164 Trichosporon isolates collected between June 2019 and December 2024 were retrospectively reviewed to assess epidemiological characteristics. A total of 68 isolates were further analyzed by intergenic spacer 1 (IGS1) sequencing, followed by phylogenetic analysis of the IGS1 region. Species identification was subsequently performed using two MALDI-TOF MS platforms: bioMérieux VITEK-MS and DL Smart MS 5020. Colony morphology was assessed after culture, and in vitro antifungal susceptibility profiles were determined. A total of 164 Trichosporon isolates from 99 patients were analyzed, with urine as the predominant specimen source (76.83

Merozoite surface protein 8 (MSP8) is a conserved blood-stage antigen implicated in erythrocyte invasion and vaccine-induced protection, but its role in coordinating host immunity during malaria remains unclear. Here, we combined MSP8 immunization, CRISPR/Cas9-mediated deletion of Plasmodium yoelii (P. yoelii) msp8, and perturbation of chemokine-receptor signaling to define how MSP8 shapes disease outcome in the lethal murine model of malaria. Mouse antisera against Plasmodium falciparum MSP8 partially inhibited merozoite invasion of human erythrocytes in vitro, and PyMSP8 immunization conferred partial protection against lethal P. yoelii 17XL challenge, supporting the notion that MSP8 functions both as an invasion-related antigen and as a target of the protective immune responses. A full-length pymsp8 knockout line (P. yoelii 17XL ΔMSP8) was generated successfully and ΔMSP8 strain infected mice exhibited reduced peak parasitemia, attenuated splenomegaly, and a self-resolving course. Transcriptomic, immunoblot, and immunohistochemical analyses revealed MSP8 deficiency upregulated chemokine CCL19 and preserved its receptor CCR7 in the spleen of infected mice, accompanied by increased IFN-γ level in spleen and serum. Functional knockdown of CCR7 using adeno-associated virus (AAV)-delivered shRNA partially abrogated the survival advantage of ΔMSP8 infection, lowered splenic CCR7 and IFN-γ levels and increased the mortality. Together, these data support a model in which parasite-expressed MSP8 is associated with reduced activity of a splenic CCL19-CCR7 axis that inducing IFN-γ-driven protective responses, whereas loss of MSP8 preserves and enhances this chemokine pathway and converts otherwise lethal infection into a self-resolving outcome. Targeting MSP8 or therapeutically augmenting CCL19-CCR7 signaling therefore represent complementary strategies for malaria vaccines and host-directed interventions.

The spleen is critically involved in the immune response to malaria parasite infections. However, the precise molecular mechanisms underlying splenic immune regulation and anemia during malaria remain elusive. This study aimed to identify the key regulatory proteins in Plasmodium yoelii (Py)-infected host spleen and investigate its role in malaria pathogenesis. Notably, significantly upregulated proteins in Py17XL-infected mice spleens were enriched in interferon (IFN) signaling, with signal transducer and activator of transcription (STAT)1, a critical component of the IFN pathway, emerging as the core molecule in the interaction network. Subsequent validation confirmed marked STAT1 upregulation in the spleens of infected hosts. Genetic ablation of STAT1 enhanced mouse survival rates and substantially reduced peripheral parasitemia post-infection and splenic parasite burden. Furthermore, STAT1 deficiency markedly reduced proportions of IFN-γ-producing CD8+ T cells and interleukin-10-producing CD4+ T cells at day 7 post-infection. Interestingly, hemoglobin concentrations and the proportion of peripheral blood reticulocytes significantly increased in STAT1-knockout mice compared with those in wild-type mice, indicating that STAT1 deficiency may alleviate malarial anemia. Altogether, the findings of this study elucidate the impact of dynamic protein changes, particularly STAT1, in the host spleen during malaria and provide a research basis for developing therapeutic interventions for malaria.IMPORTANCEThe cumulative findings demonstrate the pathogenic role of STAT1 in host spleen during Py17XL parasite infection, highlighting its role in promoting IFN-γ production and exacerbating malarial anemia. This study offers novel insights into the key pathogenic mechanisms observed in the host spleen during malaria, providing potential therapeutic targets for malaria.

Plasmodium-exported proteins bind with membrane receptors of host red blood cell to play the canonical role in erythrocyte invasion. While their potential to interact with immune cell receptors and orchestrate inflammatory responses remains largely unexplored. Among these proteins, tryptophan-rich antigens (TRAgs) participate in invading erythrocytes and demonstrate strong immunogenicity in murine malaria models. Here, we demonstrate that Plasmodium yoelii (Py) TRAg7 interacts with the macrophage receptor cluster of differentiation 71 (CD71) and activates nuclear factor kappa B p65 signaling pathway, which promoted the production of proinflammatory factors. Consistently, genetic deletion of TRAg7 led to decreased parasitemia, reduced inflammation, and improved host survival. Collectively, these findings reveal that exported proteins drive the inflammatory response by binding to macrophage receptor, expanding the current knowledge of the biological effects of malaria parasite-host interaction beyond erythrocyte invasion. This study offers a conceptual framework for better understanding malaria pathogenesis and potential therapeutic intervention strategies.

BackgroundPeritoneal dialysis-associated peritonitis (PDAP) remains a major complication in long-term dialysis patients, leading to significant morbidity and healthcare burden. This study aimed to investigate the microbial spectrum, antimicrobial resistance patterns, and clinical risk factors associated with PDAP in hospitalized patients in Anhui, China, over the past five years.MethodsA retrospective analysis was conducted on 438 peritoneal dialysis (PD) patients from three PD centers in Anhui from 2020 to early 2025. Of these, 238 patients were diagnosed with PDAP and 200 served as controls without peritonitis. Peritoneal effluents were cultured and microbiologically identified using MALDI-TOF MS and VITEK 2 systems. Antimicrobial susceptibility testing followed CLSI M100 standards. Clinical and laboratory data were statistically analyzed using SPSS v26.0, and multivariate logistic regression model was used to determine independent risk factors.ResultsSignificant differences were observed between the PDAP and control cohorts in sex, age, hospitalization time, PD duration, red blood cell count, total protein, albumin, blood glucose, and concomitant conditions (e.g., hepatitis B, autoimmune diseases, and hyperthyroidism) (p < 0.05). Laboratory infectious markers including peripheral blood white blood cell (WBC) count, neutrophil percentage, procalcitonin (PCT), C-reactive protein, peritoneal dialysate WBC and multinucleated cell counts, were significantly elevated in the PDAP population compared to controls, with serum PCT and dialysate WBCs presented as significant predictors after multivariate adjustment. Staphylococcus species showed predominant methicillin resistance (47.22% oxacillin-susceptible) with moxifloxacin outperforming other fluoroquinolones, while carbapenems demonstrated near-universal efficacy against Enterobacterales (esp., for ertapenem). Candida species mounted variable antifungal responses, with optimal activities of amphotericin B/flucytosine except fluconazole, underscoring both therapeutic opportunities and emerging resistance threats across bacterial and fungal pathogens.ConclusionThe multicenter study confirmed elevated serum PCT and peritoneal dialysate leukocytes as robust independent clinical predictors for PDAP, with other risk factors significantly increasing disease susceptibility. The diverse microbial spectrum and antimicrobial resistance features shed light on the importance of updated local microbial surveillance to guide empirical treatment and clinical management strategies on PDAP.

The apical membrane antigen-1 (AMA-1) is a potential candidate for the development of a malaria vaccine targeting Plasmodium parasites. Although studies on the immunogenicity of AMA-1 are abundant for Plasmodium falciparum and Plasmodium vivax , there is a notable scarcity of information for Plasmodium malariae . In this study, we expressed recombinant PmAMA-1 using an Escherichia coli expression system. The integrity of the rPmAMA-1 was verified through western blotting and indirect immunofluorescence assays. The immunogenic characteristics of rPmAMA-1 were assessed in BALB/c mice, utilizing the purified protein emulsified in Freund’s adjuvant. The findings revealed that mice immunized with rPmAMA-1 generated significantly elevated specific IgG antibodies, with IgG1 being the predominant component. The immune responses exhibited Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-6, and IL-10) and Th17 (IL-17a) phenotypes, but with a notable bias on Th1 response. Furthermore, the antisera against rPmAMA-1 from immunized mice enabled effective recognition of its native counterpart on P. malariae parasites, affirming the correct conformation and folding of the recombinant protein. The immune profiling study strongly suggests that PmAMA-1 would likely evoke a substantial immune response in vivo , positioning it as a promising candidate for vaccine development.

The apical membrane antigen-1 (AMA-1) is a crucial target for malaria management and prevention strategies. While the immunogenicity of AMA-1 has been extensively studied for Plasmodium falciparum and Plasmodium vivax, there is a notable scarcity of information for Plasmodium malariae. In this study, recombinant PmAMA-1 was expressed in Escherichia coli, and its integrity was confirmed via western blotting and indirect immunofluorescence assays. Immunization of BALB/c mice with rPmAMA-1 emulsified in Freund's adjuvant resulted in significantly elevated specific IgG antibodies, predominantly IgG1. The immune response exhibited Th1, Th2, and Th17 phenotypes, with a notable Th1 bias. Antisera from immunized mice effectively recognized native PmAMA-1 on P. malariae. These results suggest that PmAMA-1 is a promising target for both vaccine development and diagnostic applications for P. malariae infections, offering dual preventive and diagnostic benefits in malaria control.

BackgroundBacterium/fungus-associated pneumonia (BAP/FAP) is the prominent cause of high mortality and morbidity with important clinical impacts globally. Effective diagnostic methods and proper specimen types hopefully facilitate early diagnosis of pneumonia and prevent spread of drug-resistant bacteria/fungi among critically ill patients.MethodsIn the present study, 342 bronchoalveolar lavage fluid (BALF) samples were collected from critically ill patients with pulmonary infections between November 2020 and March 2021. The BALF materials were comparatively employed to screen BAP/FAP through microscopy, culture, antigenic marker and PCR-based methods. The limit of detection (LOD) of cultures and PCR for bacteria/fungi was determined by serial dilution assays. Specimen slides were prepared with Gram staining for microscopic examinations. Microbial cultures and identifications underwent routine clinical protocols with the aid of mass spectrometry. (1,3)-β-D-glucan and galactomannan tests with BALF were carried out accordingly. Direct detection of pathogens in BALF was achieved through PCR, followed by sequencing and BLAST in GenBank database for pathogenic identification. The subjects’ demographic and clinical characteristics were well evaluated.ResultsBAP/FAP was identified in approximately 47% of the subjects by the BALF-based PCR. The PCR-based diagnostic methods showed improved detection performance for fungi with good LOD, but performed similarly for bacteria, when compared to the cultures. There was poor agreement among traditional microscopy, culture and PCR assays for bacterial detections (kappa value, 0.184 to 0.277). For overall bacterial/fungal detections, the microscopy showed the lowest detecting rate, followed by the cultures, which displayed a slightly higher sensitivity than the microscopy did. The sensitivity of PCR was much higher than that of the other means of interest. However, the traditional cultures rather than antigenic marker-based approaches were moderately consistent with the PCR-based methods in fungal species identification, particularly for Candida and Aspergillus spp. Our findings further revealed that the age, length of hospital stay, invasive procedures and cerebral diseases were likely considered as main risk factors for BAP/FAP.ConclusionScreening for BALF in critically ill patients with suspected pneumonia pertaining high risk factors using combined PCR-based molecular detection strategies would hopefully contribute to early diagnosis of BAP/FAP and improved prognosis of the patients.

Plasmodium falciparum, mainly distributed in tropical and subtropical regions of the world, has received widespread attention owing to its severity. As a novel protein, P. falciparum surface-related antigen (PfSRA) has the structural and functional characteristics to be considered as a malaria vaccine candidate; however, limited information is available on its immunogenicity. Here, we expressed three fragments of recombinant PfSRA in an Escherichia coli system and further analyzed its immunogenicity. The results showed that rPfSRA-immunized mice produced specific antibodies with high endpoint titers (1:10,000 to 1:5,120,000) and affinity antibodies (i.e., rPfSRA-F1a (97.70%), rPfSRA-F2a (69.62%), and rPfSRA-F3a (91.87%)). In addition, the sera of immunized mice recognized both the native PfSRA and recombinant PfSRA, the rPfSRA antibodies inhibited the invasion of P. falciparum into the erythrocytes, and they were dose-dependent in vitro. This study confirmed PfSRA could be immunogenic, especially the F1a at the conserved region N-terminal and provided further support for it as a vaccine candidate against P.falciparum.

BACKGROUND:The aim of the study was to investigate the Candida species distribution and their antifungal sensitivities, clinical characteristics, and risk factors of the critically ill patients with invasive Candida infections in a tertiary hospital.METHODS:Candida strains from critically ill patients were isolated in a tertiary hospital of Anhui Province from June 2019 to June 2020 through fungal cultures and identified with MALDI-TOF MS system. The antifungal susceptibility was measured by ATB Fungus-3 method. Demographic information and laboratory data were retrieved from the computerized hospital data system.RESULTS:Candida albicans (C. albicans, 41.49%) was the predominant species in sterile body sites of critically ill patients developing invasive candidiasis, followed by C. glabrata (24.47%) and C. tropicalis (20.21%). The specimen sources were mainly urine (47.87%), then bronchoalveolar lavage fluid (18.09%) and blood (14.89%). In vitro, common Candida species were observed to be highly sensitive to amphotericin B and 5-fluorocytosine. All C. albicans exhibited susceptibility to both fluconazole and voriconazole, as did C. glabrata and C. parapsilosis. However, some C. tropicalis identified were frequently resistant to fluconazole, itraconazole, and voriconazole. The rate of Candida infection was positively correlated with certain risk factors including invasive interventions, age, length of stay in hospital, etc. Conclusions: C. albicans was the main species of invasive Candida infections in critically ill patients, followed by C. glabrata and C. tropicalis. Candida spp. showed the highest rate (10.60%) of resistance to fluconazole, followed by itraconazole (5.30%), voriconazole (5.30%), and 5-fluorocytosine (1.10%). All invasive Candida isolates were sensitive to amphotericin B. In addition, several C. tropicalis were tested and exhibited a high-level resistance to azoles. Notably, a variety of specific risk factors for candidiasis were identified in critically ill patients which need to be taken into consideration.

Background Plasmodium vivax rhoptry-associated membrane antigen (RAMA) is a glycophosphatidylinositol-anchored membrane protein currently under consideration as a malaria vaccine candidate. Immunoglobulin G (IgG) antibodies induced by P. vivax RAMA (PvRAMA) have been proved to persist over 12 months in the sera of people infected with P. vivax. It has also been shown that through stimulation of peripheral blood mononuclear cells with PvRAMA in vitro, the antigen can induce CD4 + T cells to produce interleukin-10. However, the genetic diversity of the RAMA gene in isolates of P. vivax ( pvrama ) and the immunogenicity of PvRAMA in animals remain unclear. Methods Genomic DNA was extracted from blood samples ( n = 25) of patients in Jiangsu Province, China with imported infections of P. vivax from endemic countries in South and Southeast Asia. The extract genomic DNA was used as templates to amplify the P. vivax rama gene ( pvrama ) by PCR, and the PCR products were then sequenced and analyzed by the DnaSP, MEGA, and GeneDoc software packages. Recombinant PvRAMA (rPvRAMA) protein was expressed and purified, and then used to immunize mice. Levels of total IgG and different IgG subclasses of rPvRAMA-immunized mice were evaluated by enzyme-linked immunosorbent assay. Also, spleen cells of rPvRAMA-immunized mice were stimulated with rPvRAMA in vitro and levels of T cells were measured by flow cytometry. Results The average pairwise nucleotide diversity ( π ) of the pvrama gene was 0.00190, and the haplotype diversity ( Hd ) was 0.982. The C-terminal of PvRAMA showed lower haplotype diversity compared to the N-terminal and was completely conserved at amino acid sites related to erythrocyte binding. To further characterize immunogenicity of the C-terminal of PvRAMA, mice were immunized with rPvRAMA antigen. The rPvRAMA protein induced antibody responses, with the end-point titer ranging from 1:10,000 to 1:5,120,000. IgG1 was the predominant IgG subclass in rPvRAMA-immunized mice, followed by IgG2b. In addition, levels of CD4 + and CD8 + T cells in the rPvRAMA-stimulated group were significantly higher than those in the phosphate-buffered saline-stimulated group (normal control group). Conclusions The high conservation at specific amino acid sites and the high immunogenicity of the C-terminal of PvRAMA indicate the presence of conserved epitopes able to generate broadly reactive humoral and cellular immune responses. These findings support the potential of PvRAMA to serve as a vaccine candidate against P. vivax infection. Graphical Abstract

Carbapenem resistance of Acinetobacter baumannii poses challenges to public health. Biofilm contributes to the persistence of A. baumannii cells. This study was designed to investigate the genetic relationships among carbapenem resistance, polymyxin resistance, multidrug resistance, biofilm formation, and surface-associated motility and evaluate the antibiofilm effect of polymyxin in combination with other antibiotics. A total of 103 clinical A. baumannii strains were used to determine antibiotic susceptibility, biofilm formation capacity, and motility. Enterobacterial repetitive intergenic consensus (ERIC)-PCR fingerprinting was used to determine the genetic variation among strains. The distribution of 17 genes related to the resistance-nodulation-cell division (RND)-type efflux, autoinducer-receptor (AbaI/AbaR) quorum sensing, oxacillinases (OXA)-23, and insertion sequence of ISAba1 element was investigated. The representative strains were chosen to evaluate the gene transcription and the antibiofilm activity by polymyxin B (PB) in combination with merapenem, levofloxacin, and ceftazidime, respectively. ERIC-PCR-dependent fingerprints were found to be associated with carbapenem resistance and multidrug resistance. The presence of blaOXA-23 was found to correlate with genes involved in ISAba1 insertion, AbaI/AbaR quorum sensing, and AdeABC efflux. Carbapenem resistance was observed to be negatively correlated with biofilm formation and positively correlated with motility. PB in combination with ceftazidime displayed a synergistic antibiofilm effect against robust biofilm formed by an A. baumannii strain with deficiency in AbaI/AbaR quorum sensing. Our results not only clarify the genetic correlation among carbapenem resistance, biofilm formation, and pathogenicity in a certain level but also provide a theoretical basis for clinical applications of polymyxin-based combination of antibiotics in antibiofilm therapy. IMPORTANCE Deeper explorations of molecular correlation among antibiotic resistance, biofilm formation, and pathogenicity could provide novel insights that would facilitate the development of therapeutics and prevention against A. baumannii biofilm-related infections. The major finding that polymyxin B in combination with ceftazidime displayed a synergistic antibiofilm effect against robust biofilm formed by an A. baumannii strain with genetic deficiency in AbaI/AbaR quorum sensing further provides a theoretical basis for clinical applications of antibiotics in combination with quorum quenching in antibiofilm therapy.

Background:Elizabethkingia meningoseptica is a bacterium causing potential nosocomial infections and is associated with a high mortality rate; however, the date of patients in the Hefei population who have been diagnosed with this infection is generally limited.Purpose:The clinical and laboratory data of patients from a tertiary hospital in Hefei City who had E. meningoseptica infection were evaluated in this retrospective analysis.Patients and methods:From May 2017 to November 2021, there were 24 patients infected with E. meningoseptica in the First Affiliated Hospital of Anhui Medical University. Data were gathered from the hospital's electronic medical records for all patients.Results:The most prevalent symptom among the 24 patients was fever (83.3%), followed by edema (41.7%), cough (37.5%), altered consciousness (41.7%), and sputum (37.5%), and laboratory results presented with anemia (75%), hypoproteinemia (75%), elevated C-reactive protein (CRP) (66.7%), neutrophilia (54.2%), and leukocytosis (50.0%). Hepatic disease (1 vs. 7, P = 0.009) was the only significant risk factor for underlying diseases. The mean value of lymphocyte (LYMPH#) (1.4 vs. 0.83 × 109/L, P = 0.033) counts was higher in the survival group than death group, while both anemia (8 vs. 10, P = 0.024) and hypoproteinemia (8 vs. 10, P = 0.024) occurred more frequently in the death group compared with the survival one.Conclusion:Fever was the most common symptom and the only significant factor of underlying diseases was hepatic disease (P = 0.009) that often occurred in death groups. In this investigation, the risk factors for death in patients were anemia, hypoproteinemia, and lymphocyte count. The susceptibility of some quinolones, piperacillin-tazobactam, and cotrimoxazole was relatively high, suggesting that they may be the preferred drugs for the treatment of E. meningoseptica infection. As E. meningoseptica can produce biofilm to pollute the hospital environment and cause infection in patients, the disinfection of the hospital environment should be strengthened and medical staff should pay attention to aseptic operations.

The most recent human coronaviruses including severe acute respiratory syndrome coronavirus-2 causing severe respiratory tract infection and high pathogenicity bring significant global public health concerns. Infections are initiated by recognizing host cell receptors by coronavirus spike protein S1 subunit, and then S2 mediates membrane fusion. However, human coronavirus spikes undergo frequent mutation, which may result in diverse pathogenesis and infectivity. In this review, we summarize some of these recent structural and mutational characteristics of RBD of human coronavirus spike protein and their interaction with specific human cell receptors and analyze the structural requirements and plasticity of RBD. Stability of spike protein, affinity toward receptor, virus fitness, and infectivity are the factors controlling the viral tropisms. Thus, understanding the molecular details of RBDs and their mutations is critical in deciphering virus evolution. Structural information of spike and receptors of human coronaviruses not only reveals the molecular mechanism of host-microbe interaction and pathogenesis but also helps develop effective drug to control these infectious pathogens and cope with the future emerging coronavirus outbreaks.

BACKGROUND:The imported cases of Plasmodium malariae (P. malariae) and Plasmodium ovale (P. ovale) malaria are increasing annually, especially in central China. Here, we report a case of serological rapid diagnostic test (RDT)-negative P. malariae malaria imported from West Africa.METHODS:The case patient was exclusively diagnosed with P. malariae through microscopy, Plasmodium genus-specific nested polymerase chain reaction (PCR), and sequencing of targeted P. malariae circumsporozoite (pmcsp) gene, except for serological RDT.RESULTS:The patient was discharged in stable condition after 5 days of hospitalization, with no overt malaria parasites or associated symptoms.CONCLUSIONS:This case reveals that asymptomatic P. malariae infections can occur among exported laborers back from malaria-endemic areas, some of whom may escape serological screening test or RDT, posing a continuing potential threat to malaria control. Therefore, PCR-based molecular techniques are more effective and necessary than serological RDT for malaria surveillance nationwide.

BACKGROUND:Brucellosis is currently one of the most widespread zoonotic diseases caused by Brucella genus, and the Brucella melitensis is the major pathogen. The number of people infected with Brucella has gradually increased in Anhui Province.PURPOSE:To retrospectively evaluate the epidemiological, clinical, and laboratory data of brucellosis patients in Anhui Province.PATIENTS AND METHODS:A total of 109 brucellosis patients were admitted to the First Affiliated Hospital of Anhui Medical University from January 2012 to March 2021. Data from all patients were retrieved from the hospital's electronic medical system. The final results were grouped and compared according to the presence or absence of bacteremic brucellosis and three phases of brucellosis.RESULTS:The most common symptoms among all 109 brucellosis patients were fever (89.0%), followed by chills (52.3%), arthralgia (48.6%), and weight loss (30.3%), and laboratory results presented with anemia (65.1%), elevate of C-reactive protein (CRP) (91.7%), erythrocyte sedimentation rate (ESR) (86.2%), aspartate aminotransferase (AST) (40.4%), and lactate dehydrogenase (LDH) (43.1%). The percentage of fever (96.1%), arthralgia (58.8%), anorexia (35.3%), leukopenia (31.4%), and the AST (51.0%) were higher in bacteremic than nonbacteremic group. Additionally, the median level of LDH (332.0 mg/L, IQR, 209.0-553.0) was higher in bacteremic than nonbacteremic group. Nevertheless, the albumin (36.0 mg/L, IQR, 33.9-38.2) was lower in the bacteremic group. The percentage of fever (94.9%) and the median LDH level (316.0 U/L (IQR,218.0-517.5)) in the acute phase of brucellosis were higher than the percentage of fever (72.0%) and the median LDH level (209.0 U/L (IQR,162.0-276.0)) in the subacute phase of brucellosis.CONCLUSION:Brucellosis has become an important public health issue in Anhui Province. Brucellosis is a disease with diverse clinical manifestations. Our data showed that unexplained fever, arthralgia, and elevated AST and LDH should be considered as a diagnosis of bacteremia brucellosis for early treatment intervention.

Plasmodium vivax–infected erythrocytes can enter the spleen and evade spleen clearance to establish chronic infections. However, the mechanism underlying P. vivax immune evasion in the spleen is still unclear. Human splenic fibroblasts (HSF), also known as barrier cells, play an essential role in the immune function of spleen. A hypothesis holds that P. vivax—infected erythrocytes induce spleen structural remodeling to form barrier cells. Subsequently, these infected erythrocytes can selectively cytoadhere to these barrier cells to escape spleen clearance. In this work, we found that P. vivax surface-related antigen (PvSRA; PlasmoDB ID: PVX_084970), an exported protein on infected erythrocyte membrane, could bind with HSF. Considering the above hypothesis, we speculated that PvSRA might be involved in P. vivax immune evasion by changing HSF cell performance. To investigate this speculation, RNA sequencing, protein microarray, and bioinformatics analysis technologies were applied, and in vitro validations were further performed. The results showed that the recombinant PvSRA attracted HSF migration and interacted with HSF by targeting integrin β1 (ITGB1) along with changes in HSF cell performance, such as focal adhesion, extracellular matrix, actin cytoskeleton, and cell cycle. This study indicated that PvSRA might indeed participate in the immune evasion of P. vivax in the spleen by changing HSF function through PvSRA–ITGB1 axis.

Background: The clinical diagnosis and therapy for ICU patients with invasive candidiasis are challenged by the changes of Candida community composition and antimicrobial resistance. The epidemiology and drug sensitivity of candidiasis in ICU as well as its risk factors and drug resistance mechanism were investigated. Methods: In the present study, 115 patients in ICU were recruited from June 2019 through July 2020. Among them, 83 Candida isolates were identified with MALDI-TOF mass spectrometry. The susceptibility to antifungals was measured by microdilution method. The molecular mechanisms of azole-resistant Candida tropicalis were explored by sequencing, and their outcomes were explicitly documented. Results: Candida glabrata and C. tropicalis were the predominant non-C. albicans Candida. The specimen sources were mainly urine, bronchoalveolar lavage fluid and blood. The age, length of hospitalization, tracheotomy, diabetes and concomitant bacterial infection were the main risk factors for candidiasis. The majority of Candida species exhibited susceptibility to antifungals. However, certain C. tropicalis were frequently resistant to azoles. The polymorphism of the ERG11 in C. tropicalis was likely associated with azole resistance. Conclusion: The multiple risk factors for candidiasis in ICU patients need to be considered. Certain C. tropicalis exhibit resistance to azoles likely due to the ERG11 gene polymorphism.

With the rapid growth of antibiotic-resistant bacteria, it is urgent to develop alternative therapeutic strategies. Pore-forming toxins (PFTs) belong to the largest family of virulence factors of many pathogenic bacteria and constitute the most characterized classes of pore-forming proteins (PFPs). Recent studies revealed the structural basis of several PFTs, both as soluble monomers, and transmembrane oligomers. Upon interacting with host cells, the soluble monomer of bacterial PFTs assembles into transmembrane oligomeric complexes that insert into membranes and affect target cell-membrane permeability, leading to diverse cellular responses and outcomes. Herein we have reviewed the structural basis of pore formation and interaction of PFTs with the host cell membrane, which could add valuable contributions in comprehensive understanding of PFTs and searching for novel therapeutic strategies targeting PFTs and interaction with host receptors in the fight of bacterial antibiotic-resistance.

Background Human listeriosis is a severe foodborne infection caused by Listeria monocytogenes and the data of patients with this infection are largely limited for the Hefei population. Purpose This is a retrospective study that evaluated the clinical and laboratory data of patients with listeriosis at a tertiary hospital in Hefei City. Patients and Methods A total of 24 listeriosis patients were admitted to the First Affiliated Hospital of Anhui Medical University from January 2003 to July 2021. Data from all patients were collected from the hospital’s electronic medical records. Results The most common symptom of all patients was fever (91.7%), followed by altered consciousness (50.0%), rashes (45.8%), respiratory distress symptoms (37.5%), nuchal rigidity (29.2%), and headaches (20.8%). Laboratory results also indicated elevated C-reactive protein (CRP) (79.1%), hypoproteinemia (75.0%), anemia (62.5%), leukocytosis (45.8%), and neutrophilia (45.8%). The mean value of 5.1 μg/mL (SD, 3.8) for D‐dimer (D‐D) was significantly higher than the normal value ((0.00–0.50) μg/mL), while both altered consciousness (6 vs 4, P = 0.034) and headaches (4 vs 1, P = 0.036) occurred more frequently in the neurolisteriosis group compared with the bacteremia one. Additionally, the mean maximal body temperature (°C) (40.5 ± 0.7) as well as white blood cell (WBC) (15.3 vs 7.5 ×109/L, P = 0.014) and neutrophil (NEUT#) (13.2 vs 6.1 ×109/L, P = 0.026) counts of neurolisteriosis patients were higher than those of bacteremia (39.4 ± 0.4) (P = 0.001). Of all patients, four (50%) from the maternal-neonatal group remained uncured. Conclusion Listeriosis is a rare disease with extremely variable clinical characteristics in Hefei City. Our data indicated that unexplained fever, altered consciousness, hypoproteinemia, anemia, elevated CRP and DD should be considered to assist diagnosis of listeriosis for early treatment interventions.