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Bacterial infection often results in the formation of tissue abscesses, which represent the primary site of interaction between invading bacteria and the innate immune system. We identify the host protein calprotectin as a neutrophil-dependent factor expressed inside Staphylococcus aureus abscesses. Neutrophil-derived calprotectin inhibited S. aureus growth through chelation of nutrient Mn²⁺ and Zn²⁺: an activity that results in reprogramming of the bacterial transcriptome. The abscesses of mice lacking calprotectin were enriched in metal, and staphylococcal proliferation was enhanced in these metal-rich abscesses. These results demonstrate that calprotectin is a critical factor in the innate immune response to infection and define metal chelation as a strategy for inhibiting microbial growth inside abscessed tissue.

Liver abscesses are a significant concern in cattle feeding, linked to visceral condemnation and carcass trimming; however, the molecular mechanism of development and progression of liver abscesses is unknown. This study aimed to evaluate the hepatic transcriptomic profile, immunohistochemistry, and IGF-I circulation in beef × dairy (Angus × Holstein) steers with and without liver abscesses. Samples were collected from twelve steers (final body weight of 719 ± 5.8 kg) originating from the same feedlot and were selected based on liver scores at harvest. The animals were divided into abscessed ( n  = 6) and healthy livers ( n  = 6). Blood samples were used to measure circulating insulin-like growth factor I (IGF-I) levels using an ELISA kit. Liver samples were divided into two portions; one portion was used for immunohistochemistry (IHC) to identify IGF-I receptor (IGF-IR) abundance, while the second portion was used for RNA extraction, library preparation, and sequencing (Illumina NovaSeq 6000 platform). Differentially expressed genes (DEGs) were identified with the DESeq2 R package, using an adjusted p -value ≤ 0.05 and fold change > 1.5. Sera IGF-I was not affected by liver condition; however, IGF-IR abundance was up-regulated in abscessed livers. A total of 568 DEGs were identified, with 372 up-regulated and 196 down-regulated in abscessed livers. Notably, the most highly up-regulated genes were FGF23 , NXPH4 , and CYP7A1 , while EPHA6 , CD70 , and INHBA showed the most significant downregulation. Protein-protein interaction (PPI) network analysis identified THBS1 and COL1A2 as significant hub genes. The DEGs showed enrichment in biological processes related to angiogenesis, cell migration, adhesion, and extracellular matrix organization. Pathway analysis indicated activation in signaling pathways, including hepatic fibrosis, interleukin, and IGF-I signaling. These findings reveal candidate genes and pathways linked to inflammatory responses and tissue remodeling, offering valuable evidence that enhances our understanding of the progression of liver abscesses in cattle.

The global incidence of invasive Klebsiella pneumoniae liver abscess syndrome (IKPLAS) increases, yet its underlying molecular mechanisms remain elusive, hindering the development of effective therapeutic strategies. In this study, we analyze bacterial molecular profiles and clinical data from patients with KPLA and IKPLAS, and find no significant difference in the molecular characteristics of K. pneumoniae between the two groups, however, we identify elevated blood lactate levels as an independent predictor of IKPLAS. Further investigation reveals that lactate enhances K. pneumoniae virulence by promoting capsular polysaccharide (CPS) biosynthesis. Mechanistically, lactate reduces cyclic adenosine monophosphate (cAMP) levels by downregulating the expression of mannose-specific phosphotransferase system (man-PTS) enzyme IIA-D genes ( gfrA , gfrB, gfrC and gfrD ). This reduction in cAMP levels enhances CPS biosynthesis by decreasing its binding to the cAMP receptor protein (CRP). Our results highlight lactate’s role in enhancing the virulence of K. pneumoniae via the PTS-CRP axis, offering insights into the pathogenesis of IKPLAS. The molecular mechanism for invasive Klebsiella pneumoniae liver abscess syndrome (IKPLAS) remains poorly studied. Here, the authors demonstrate that the elevated blood lactate level is an independent predictor of IKPLAS by enhancing the virulence of K. pneumoniae via the PTS-CRP axis.

Invasive liver abscess (ILA) represents a formidable clinical challenge, characterized by rapidly evolving hepatic lesions and systemic dissemination. The gut–liver axis, a vital conduit for immune and metabolic regulation, has emerged as a central driver of its pathogenesis. This narrative review draws on insights from select transcriptomic, proteomic, metabolomic, and microbiomic studies, revealing how chronic antibiotic use, unhealthy diets, and lingering pathological conditions disrupt intestinal barrier integrity and perturb bile acid and short-chain fatty acid metabolism. This dysregulated microenvironment facilitates bacterial translocation into the liver, triggering a robust inflammatory cascade and the upregulation of virulence factors involved in capsule synthesis and biofilm formation. Evidence suggests microbial dysbiosis contributes to hepatic immune dysregulation. These insights pave the way for novel ILA interventions. This review offers original insights by critically integrating evidence from transcriptomic, proteomic, metabolomic, and microbiomic studies with GRADE-evaluated clinical data, proposing a novel bacteria–inflammation–virulence feedback loop and precision therapeutic frameworks that target the gut-liver axis, filling gaps in traditional ILA models and guiding future interventions.

Background Klebsiella pneumoniae is considered the most clinically relevant species of Enterobacteriaceae, known to cause severe infections including liver abscesses. To the best of our knowledge, a large proportion of iron in the human body is accumulated and stored in the liver. We hypothesize that increased iron availability is an important factor driving liver abscess formation and we therefore aim to understand the effects of iron on K. pneumoniae causing liver abscesses. Results All tested K. pneumoniae clinical isolates, including those isolated from liver abscesses and other abdominal invasive infection sites, grew optimally when cultured in LB broth supplemented with 50 μM iron and exhibited the strongest biofilm formation ability under those conditions. Decreased growth and biofilm formation ability were observed in all tested strains when cultured with an iron chelator ( P  < 0.05). The infection model of G. mellonella larvae indicated the virulence of liver abscess-causing K. pneumoniae (2/3) cultured in LB broth with additional iron was significantly higher than those under iron-restricted conditions ( P  < 0.05). The relative expression levels of the four siderophore genes ( iucB , iroB , irp1 , entB ) in K. pneumoniae strains isolated from liver abscesses cultured with additional iron were lower than those under iron-restricted conditions ( P  < 0.05). Conclusions It is suggested by our research that iron in the environment can promote growth, biofilm formation and enhance virulence of K. pneumoniae causing liver abscesses . A lower expression of siderophore genes correlates with increased virulence of liver abscess-causing K. pneumoniae . Further deeper evaluation of these phenomena is warranted.

Malnutrition substantially increases susceptibility to Entamoeba histolytica in children. Leptin is a hormone produced by adipocytes that inhibits food intake, influences the immune system, and is suppressed in malnourished children. Therefore we hypothesized that diminished leptin function may increase susceptibility to E. histolytica infection. We prospectively observed a cohort of children, beginning at preschool age, for infection by the parasite E. histolytica every other day over 9 years and evaluated them for genetic variants in leptin (LEP) and the leptin receptor (LEPR). We found increased susceptibility to intestinal infection by this parasite associated with an amino acid substitution in the cytokine receptor homology domain 1 of LEPR. Children carrying the allele for arginine (223R) were nearly 4 times more likely to have an infection compared with those homozygous for the ancestral glutamine allele (223Q). An association of this allele with amebic liver abscess was also determined in an independent cohort of adult patients. In addition, mice carrying at least 1 copy of the R allele of Lepr were more susceptible to infection and exhibited greater levels of mucosal destruction and intestinal epithelial apoptosis after amebic infection. These findings suggest that leptin signaling is important in mucosal defense against amebiasis and that polymorphisms in the leptin receptor explain differences in susceptibility of children in the Bangladesh cohort to amebiasis.

The disease state of amebiasis, caused by Entamoeba histolytica, varies from asymptomatic to severe manifestations that include dysentery and extraintestinal abscesses. The virulence factors of the pathogen, and host defense mechanisms, contribute to the outcomes of infection; however, the underlying genetic factors, which affect clinical outcomes, remain to be fully elucidated. To identify these genetic factors in E. histolytica, we used Illumina next-generation sequencing to conduct a comparative genomic analysis of two clinical isolates obtained from diarrheal and asymptomatic patients (strains KU50 and KU27, respectively). By mapping KU50 and KU27 reads to the genome of a reference HM-1:IMSS strain, we identified two genes (EHI_089440 and EHI_176590) that were absent in strain KU27. In KU27, a single AIG1 (avrRpt2-induced gene 1) family gene (EHI_176590) was found to be deleted, from a tandem array of three AIG1 genes, by homologous recombination between the two flanking genes. Overexpression of the EHI_176590 gene, in strain HM-1:IMSS cl6, resulted in increased formation of cell-surface protrusions and enhanced adhesion to human erythrocytes. The EHI_176590 gene was detected by PCR in 56% of stool samples from symptomatic patients infected with E. histolytica, but only in 15% of stool samples from asymptomatic individuals. This suggests that the presence of the EHI_176590 gene is correlated with the outcomes of infection. Taken together, these data strongly indicate that the AIG1 family protein plays a pivotal role in E. histolytica virulence via regulation of host cell adhesion. Our in-vivo experiments, using a hamster liver abscess model, showed that overexpression or gene silencing of EHI_176590 reduced and increased liver abscess formation, respectively. This suggests that the AIG1 genes may have contrasting roles in virulence depending on the genetic background of the parasite and host environment.

Amebic liver abscess (ALA), a parasitic disease due to infection with the protozoan Entamoeba histolytica, occurs age and gender dependent with strong preferences for adult males. Using a mouse model for ALA with a similar male bias for the disease, we have investigated the role of female and male sexual hormones and provide evidence for a strong contribution of testosterone. Removal of testosterone by orchiectomy significantly reduced sizes of abscesses in male mice, while substitution of testosterone increased development of ALA in female mice. Activation of natural killer T (NKT) cells, which are known to be important for the control of ALA, is influenced by testosterone. Specifically activated NKT cells isolated from female mice produce more IFNγ compared to NKT cells derived from male mice. This high level production of IFNγ in female derived NKT cells was inhibited by testosterone substitution, while the IFNγ production in male derived NKT cells was increased by orchiectomy. Gender dependent differences were not a result of differences in the total number of NKT cells, but a result of a higher activation potential for the CD4(-) NKT cell subpopulation in female mice. Taken together, we conclude that the hormone status of the host, in particular the testosterone level, determines susceptibility to ALA at least in a mouse model of the disease.

We sought to establish an ex vivo model for examining the interaction of E. histolytica with human tissue, using precision-cut liver slices (PCLS) from donated organs. E. histolytica- or E. dispar-infected PCLS were analyzed at different post-infection times (0, 1, 3, 24 and 48 h) to evaluate the relation between tissue damage and the expression of genes associated with three factors: a) parasite survival (peroxiredoxin, superoxide dismutase and 70 kDa heat shock protein), b) parasite virulence (EhGal/GalNAc lectin, amoebapore, cysteine proteases and calreticulin), and c) the host inflammatory response (various cytokines). Unlike E. dispar (non-pathogenic), E. histolytica produced some damage to the structure of hepatic parenchyma. Overall, greater expression of virulence genes existed in E. histolytica-infected versus E. dispar-infected tissue. Accordingly, there was an increased expression of EhGal/GalNAc lectin, Ehap-a and Ehcp-5, Ehcp-2, ehcp-1 genes with E. histolytica, and a decreased or lack of expression of Ehcp-2, and Ehap-a genes with E. dispar. E. histolytica-infected tissue also exhibited an elevated expression of genes linked to survival, principally peroxiredoxin, superoxide dismutase and Ehhsp-70. Moreover, E. histolytica-infected tissue showed an overexpression of some genes encoding for pro-inflammatory interleukins (ILs), such as il-8, ifn-γ and tnf-α. Contrarily, E. dispar-infected tissue displayed higher levels of il-10, the gene for the corresponding anti-inflammatory cytokine. Additionally, other genes were investigated that are important in the host-parasite relationship, including those encoding for the 20 kDa heat shock protein (HSP-20), the AIG-1 protein, and immune dominant variable surface antigen, as well as for proteins apparently involved in mechanisms for the protection of the trophozoites in different environments (e.g., thioredoxin-reductase, oxido-reductase, and 9 hypothetical proteins). Some of the hypothetical proteins evidenced interesting overexpression rates, however we should wait to their characterization. This finding suggest that the present model could be advantageous for exploring the complex interaction between trophozoites and hepatocytes during the development of ALA, particularly in the initial stages of infection.

Amoebic liver abscess (ALA) is the most common extraintestinal amoebiasis caused by Entamoeba histolytica (E. histolytica). However, despite current knowledge and scientific advances about this infection, there are no effective treatments to prevent it. Herein, the antiamoebic capacity of curcumin in a hamster model was evaluated. Curcumin (150 mg/kg, p.o., daily during 10 days before infection) considerably prevents liver damage induced at 12 and 48 h post-intrahepatic inoculation of trophozoites and decreases ALT, ALP, and γ-GTP activities, and macroscopic and microscopic observations were consistent with these results. On the other hand, after one week of intraportal inoculation, liver damage was prevented by curcumin (150 mg/kg, p.o., daily, 20 days before amoebic inoculation and during the week of infection); liver/body weight ratios and tissue and histological stains showed normal appearance; in addition, the increases in ALT, ALP, and γ-GTP activities were prevented; the depletion of glycogen content induced by the amoebic damage was partially but significantly prevented, while NF-κB activity was inhibited and the expression of IL-1β was reduced; Nrf2 production showed a tendency to increase it, and HO-1 protein was overexpressed. These results suggest for the first time that curcumin can be a compound with antiamoebic effect in the liver, suggesting that its daily use could help greatly decrease the incidence of this type of infection.