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. 2025 Sep 23;15(1):32644.
doi: 10.1038/s41598-025-10093-z.

Exploring the dynamic relationship between antimicrobial resistance, virulence fitness, and host responses in Listeria monocytogenes infections

Nada K Alharbi  1 , Marwa I Abd El-Hamid  2 , Naglaa F S Awad  3 , Reham M El-Tarabili  4 , Sara T Elazab  5 , Rasha A Mosbah  6 , Arwa R Elmanakhly  7 , Majid Alhomrani  8   9 , Abdulhakeem S Alamri  8   9 , Norah K Algarzae  10 , Musaad B Alsahly  10 , Thamer A Alsufayan  10 , Basma A Fakhary  11 , Maha Alharbi  1 , Mahmoud M Bendary  12
Affiliations

Exploring the dynamic relationship between antimicrobial resistance, virulence fitness, and host responses in Listeria monocytogenes infections

Nada K Alharbi et al. Sci Rep. .

Abstract

Listeriosis is a severe zoonotic disease caused by Listeria monocytogenes (L. monocytogenes), which can be acquired through animal source foods. This pathogen shows unique virulence fitness allowing it to penetrate and survive inside host cells causing extremely dangerous symptoms. Therefore, we aimed to correlate the clinical outcomes with the antimicrobial resistance and virulence profiles of L. monocytogenes. This is crucial for improving disease management, developing new therapeutic strategies, enhancing public health and food safety, and advancing scientific knowledge. Therefore, we assessed the antimicrobial resistance and virulence profiles of L. monocytogenes isolated from various sources, along with their potential to cause disease, using an in vivo rabbit model. Based on identification criteria, 47 L. monocytogenes isolates (15. 7%) were recovered with the highest detection rates among rabbits (22%). Unfortunately, all the investigated isolates showed multidrug resistance (MDR) as well as multi-virulent profiles with 45 highly heterogeneous clusters. Noteworthy, the degree of illnesses of the experimentally infected rabbits was dependent on the virulence profiles. Specific nervous manifestations and severe histopathological alterations were observed in experimental rabbits infected with highly virulent isolates confirming that the potential ability of this pathogen to produce a disease is not always decipherable from its virulence arrays. Finally, it was confirmed that managing infections caused by L. monocytogenes has become increasingly challenging due to its high antimicrobial resistance, strong virulence, and the severe pathological effects linked to its virulence factors. VSports手机版.

Keywords: L. monocytogenes; Pathogenicity; Rabbits; Resistance; Virulence; Zoonotic. V体育安卓版.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the ethical principles set forth by the Research Ethics Committee of Egypt’s Suez Canal University. The Ethics Review Committee (AERC-SCU) approved both the animal handling procedures and the collection of human samples under approval number SCU2023070. Consent for publication: were applicable and available up on demand. Competing interests: The authors declare no competing interests V体育ios版.

Figures

Fig. 1
Fig. 1
Detection rates of L. monocytogenes isolates across various sample sources. It showed the detection rates of L. monocytogenes isolates in samples collected from different sources, including animals (red circles), chicken (green triangles), food (blue squares), and humans (purple crosses). The size of the markers represented the detection percentage within each sample type.
Fig. 2
Fig. 2
Antimicrobial resistance profiles and distribution across sample types. (A) Percentage distribution of Listeria monocytogenes isolates showing resistance (blue) and sensitivity (red) to various antimicrobial agents. FOX: cefoxitin, PEN: penicillin, AMP: ampicillin, SAM: ampicillin-sulbactam, OXA: oxacillin, GEN: gentamicin, KAN: kanamycin, ENR: enrofloxacin, ERY: erythromycin, CLI: clindamycin, VAN: vancomycin, TET: tetracycline, CHL: chloramphenicol, RIF: rifampicin, SXT: trimethoprim-sulfamethoxazole. (B) Heatmap showing the number of antimicrobial classes to which L. monocytogenes isolates exhibited resistance across different sample types (chicken liver, rabbit ear swabs, cattle milk, sheep milk, pregnant women’s stool, and food). (C) Heatmap indicating the number of individual antimicrobial drugs to which resistance was detected in each sample type. (D) Heatmap illustrating the Multiple Antibiotic Resistance (MAR) index values across the various sample types, reflecting the extent of resistance burden.
Fig. 3
Fig. 3
Prevalence and distribution of virulence genes in Listeria monocytogenes isolates. (A) Radar chart showing the overall prevalence (%) of major virulence genes detected among L. monocytogenes isolates. The genes include inlA, inlB, prfA, hlyA, actA, vip, lap, bilE, inlF, inlP, pplA, and arcA. The shaded area represents the relative frequency of each gene across all isolates. (B) Heatmap illustrating the distribution of virulence genes across different sample sources, including chicken liver, rabbit ear swabs, cattle milk, sheep milk, pregnant women’s stool, and food samples. The color scale represents the prevalence (%) of each gene within isolates from each sample type. Virulence gene abbreviations: prfA (transcriptional activator), hlyA (listeriolysin O), inl (internalin), iap (invasion-associated protein), vip (intracellular proliferation factor), lap (adhesion protein), bilE (bile resistance gene), inlF (internalization protein), inlP (internalin-like protein), pplA (proteinase-like protein A), arcA (anoxic respiratory control), and actA (actin assembly-inducing protein).
Fig. 4
Fig. 4
Distribution of virulence and antibiotic resistance genes in L. monocytogenes isolates and their correlation analysis. (A) Heatmap showing the presence (red) and absence (blue) of virulence genes and resistance profiles to various antibiotics across L. monocytogenes isolates from different sample types. The columns represent either virulence genes (e.g., hlyA, prfA, actA) or antimicrobial agents, while the rows represent individual isolates. Hierarchical clustering is applied to group isolates based on similarity in genetic and resistance profiles. Sample source codes on the right side of the heatmap are abbreviated as follows: SM (sheep milk), CM (cattle milk), CL (chicken liver), RS (rabbit swabs), HS (human stool), S (sausage), L (luncheon), B (burger), C (cheese), and MM (minced meat). (B) Correlation matrix between virulence genes and antibiotic resistance profiles. Positive correlations are shown in red and negative correlations in blue. The values within the grid represent correlation coefficients (r), with darker shades indicating stronger relationships. Antibiotic abbreviations: AMP (ampicillin), KAN (kanamycin), ENR (enrofloxacin), ERY (erythromycin), VAN (vancomycin), TET (tetracycline), CHL (chloramphenicol), SXT (trimethoprim-sulfamethoxazole). Virulence gene abbreviations: prfA (transcriptional activator), hlyA (listeriolysin O), inl (internalin), iap (invasion-associated protein), vip (intracellular proliferation factor), lap (adhesion protein), bilE (bile resistance gene), inlF (internalization protein), inlP (internalin-like protein), pplA (proteinase-like protein A), arcA (anoxic respiratory control), and actA (actin assembly-inducing protein).
Fig. 5
Fig. 5
Comparative macroscopic examination of healthy and post-infection rabbits. Clinical signs (A–C) and postmortem lesions (D–G) of rabbits post experimental infection with L. monocytogenes isolates in the form of ruffled fur (A), diarrhea soiled the hind quarters (B), conjunctivitis (C) and marked congestion in spleen (D), brain blood vessels (E), liver (F) and lung (G), normal spleen (H), normal brain blood vessels (I), normal liver (J) and normal lung (K).
Fig. 6
Fig. 6
Liver sections of rabbits experimentally infected with L. monocytogenes. Section A shows the liver Section 7 days post-infection, while section B shows the liver Section 14 days post-infection. The eight L. monocytogenes isolates (1–8) were shown in both sections. 1A: focal interstitial aggregations of round cells (arrow head), 1B: minute interstitial round cells’ aggregations (arrow), 2A: moderate congestion of hepatic blood vessels with periportal round cells’ aggregations (arrow head) and early necrotic changes within some hepatocytes (arrow), 2B: widely distributed areas of hydropic degeneration (arrow head), portal area with fibroplasia (star) and bile stasis (arrow), 3A: degenerative (curved arrow) and necrotic (arrow) changes of hepatic parenchyma with interstitial minute round cells (arrow head), 3B: degenerative (curved arrow) and necrotic (arrow head) changes in hepatic parenchyma besides congestion of some portal blood vessels (arrow), 4A: number of apoptotic hepatocytes (arrow head), 4B: degenerative changes of hepatic parenchyma, necrosis of some hepatocytes (curved arrow) and bile stasis within bile duct lumen (arrow), 5A: congestion of hepatic blood vessels (arrows) and degenerative changes mainly hydropic degeneration and steatosis (arrow heads), 5B: mild congestion (arrow head) of hepatic parenchyma, 6A: perivascular minute area of necrosis infiltrated by inflammatory cells (arrow), 6B: minute interstitial round cells infiltration and distributed apoptotic cells (arrow) within hepatic parenchyma, 7A: some mildly congested blood vessels (arrow), 7B: hydropic degeneration of large number of hepatic parenchyma (arrow head), 8A: mildly congested blood vessels and minute perivascular leucocytic aggregations (arrow) and 8B: apparently normal hepatic parenchyma (arrow head).
Fig. 7
Fig. 7
Brain sections of rabbits experimentally infected with L. monocytogenes. Section A shows the brain Section 7 days post-infection, while section B shows the brain Section 14 days post-infection. The eight L. monocytogenes isolates (1–8) were shown in both sections. 1A: congested cerebral blood vessels (arrow) and few numbers of degenerated neurons with satellitosis (arrow head), 1B: some hemorrhagic areas (arrow head). 2A: apparently normal nerve cell bodies (arrow heads), neuropil and cerebral vasculature (arrow head), 2B: normal brain tissue with few degenerated neurons (arrow head). 3A: number of degenerated neurons surrounded by glia cells (arrow head), 3B: prominent perivascular cuff (arrow heads), 4A: inflammatory cells infiltration in periventricular tissue (curved arrow), ventricular congestion (arrow), degenerative changes of some neurons (arrow head) and parenchymal bleeding (thick arrow), 4B: degenerated neurons within cerebral parenchyma (arrow). 5A: congested meningeal blood vessels (arrow) with perivascular edema (star), 5B: preserved neurons (arrow head), glia cells and neuropils in most brain parenchyma, 6A: congestion of meningeal blood vessels (arrow) and perivascular lymphocytic aggregations (arrow head), 6B: dilated meningeal blood vessels (arrow) and inflammatory cells infiltration (arrow head), 7A: extravasated erythrocytes within Virchow robin space (arrow head), 7B: dilated cerebral blood vessels (arrow) and perivascular minute aggregations of inflammatory cells (arrow head), 8A: dilated meningeal blood vessels, extravasated erythrocytes (arrow), mixture of monocytes/macrophages and neutrophils (curved arrow) in meninges and satellitosis (arrow head) in brain parenchyma and 8B: extravasated erythrocytes within Virchow robin space (arrow head) and aggregation of glia cells around some degenerated neurons (arrow).
Fig. 8
Fig. 8
Spleen sections of rabbits experimentally infected with L. monocytogenes. Section A shows the spleen Section 7 days post-infection, while section B shows the spleen Section 14 days post-infection. The eight L. monocytogenes isolates (1–8) were shown in both sections. 1A: mild depleted lymphoid aggregations of splenic white pulps (arrow head), 1B: some apoptotic changes (curved arrow) within white pulp, 2A: apparently normal lymphoid elements of white pulp with central arteriole (arrow head) and splenic sinusoids of red pulp, 2B: relatively normal central arteriole (arrow head), lymphoid follicles and dilated sinusoids with erythrocytes (curved arrow), 3A: apparently normal hemopiotic elements, central arteriole (arrow head) and splenic sinusoids with number of inflammatory cells (star), 3B: normal lymphoid follicles and dilated splenic sinusoids (arrow), 4A: mildly depleted lymphoid follicle (arrow), 4B: apparently normal splenic parenchyma with number of inflammatory cells within splenic sinusoids (arrow), 5A: apparently normal lymphoid structures and vasculature (arrow head), 5B: mild depletion of lymphoid population of the white pulp (arrow) and infiltration of dilated sinusoids by large number activated macrophages (arrow head), 6A: apparently normal white pulp (arrow) with central arteriole (arrow head) and red pulp with sinusoids, 6B: dilated central arteriole (arrow head) with preserved white and red pulp, 7A: hypo cellular white pulp lymphoid follicles (arrow) and dilated sinusoids (arrow head), 7B: depleted lymphoid elements of splenic white pulp (arrow), 8A: apoptotic lymphoid elements of white pulp (arrow) and 8B: mildly dilated central arteriole (arrow head) with apoptotic lymphoid elements (arrow).
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