# Analysis of Potential Genes, Acute Phase Proteins and Hormonal Profiles Associated with Methicillin-Resistant Staphylococcus aureus (MRSA) Isolation from Pneumonic Sheep

**Authors:** Hanan M. Alharbi, Eman A. Noaman, Ahmed El-Sayed, Mohamed T. Ragab, Amani Hafez, Attia Eissa, Ahmed Ateya, Khairiah M. Alwutayd, Manal A. Babaker, Asmaa Darwish

PMC · DOI: 10.3390/vetsci12060584 · 2025-06-13

## TL;DR

This study examines genes, proteins, and hormones in sheep with pneumonia caused by MRSA, revealing differences that could help understand and manage the infection.

## Contribution

The study identifies specific gene expression patterns and biochemical markers associated with MRSA in pneumonic sheep.

## Key findings

- MRSA isolates showed complete resistance to amoxicillin, cloxacillin, and erythromycin but remained susceptible to vancomycin.
- Genes like TLR2, CLEC4E, PTX3, CXCL8, and IL15RA were upregulated in pneumonic sheep, while SOCS3 was downregulated.
- Pneumonic sheep had elevated acute phase proteins, cortisol, and growth hormone, with reduced insulin, T3, and T4 levels.

## Abstract

Staphylococcus aureus is a significant bacterial pathogen responsible for a wide range of infections in both humans and animals. In this study, 100 pneumonic sheep and 100 clinically healthy sheep were examined to assess biochemical parameters and gene expression profiles. The findings revealed notable differences in gene expression, nucleotide sequences, and biochemical markers between healthy and pneumonic animals. Additionally, MRSA isolates displayed complete resistance to amoxicillin, cloxacillin, and erythromycin, along with high resistance to penicillin and tetracycline. However, all MRSA isolates remained fully susceptible to vancomycin. The observed alterations in molecular and biochemical marker profiles may contribute to the pathogenesis and clinical manifestations of pneumonia in sheep.

Staphylococcus aureus is a significant bacterial pathogen responsible for a wide range of diseases in both humans and animals. This study aimed to investigate nucleotide sequence variations, gene expression patterns, and serum biomarkers, including acute phase proteins (APPs), hormonal fluctuations, and iron profile parameters in sheep affected by pneumonia. Additionally, the study focused on the isolation and characterization of S. aureus from pneumonic sheep, with particular emphasis on the prevalence of methicillin-resistant S. aureus (MRSA) strains. Blood samples were collected from both healthy and pneumonic sheep for gene expression and biochemical analyses, while nasal swabs from pneumonic sheep were used for bacterial isolation and identification. Out of 100 nasal swabs analyzed, 44% tested positive for Staphylococcus spp., and 61.4% of these were confirmed as S. aureus by PCR. The mecA gene, a key marker of methicillin resistance, was identified in 17 isolates (38.6% of the S. aureus-positive samples). MRSA isolates showed complete resistance to amoxicillin, cloxacillin, and erythromycin, and high resistance to penicillin, amoxicillin, and tetracycline; however, all MRSA strains remained fully susceptible to vancomycin. Gene expression analysis revealed that TLR2, CLEC4E, PTX3, CXCL8, and IL15RA were significantly upregulated (p < 0.05) in pneumonic ewes, while SOCS3 expression was markedly downregulated. Sequence analysis of immune-related genes revealed notable nucleotide differences between healthy and affected animals. Furthermore, the pneumonic group exhibited significantly elevated levels of APPs, cortisol, and growth hormone, along with reduced levels of insulin, T3, and T4. These findings underscore the zoonotic risk posed by MRSA and emphasize the need for robust surveillance and antibiotic stewardship to control its spread. The study also highlights the importance of molecular diagnostics in accurately identifying MRSA and elucidating resistance mechanisms, thereby facilitating targeted treatment and informed management strategies.

## Linked entities

- **Genes:** TLR2 (toll like receptor 2) [NCBI Gene 7097], CLEC4E (C-type lectin domain family 4 member E) [NCBI Gene 26253], PTX3 (pentraxin 3) [NCBI Gene 5806], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576], IL15RA (interleukin 15 receptor subunit alpha) [NCBI Gene 3601], SOCS3 (suppressor of cytokine signaling 3) [NCBI Gene 9021], mecA (adaptor protein controlling oligomerization of the AAA+ protein ClpC) [NCBI Gene 936406]
- **Proteins:** PIN (insulin precursor)
- **Chemicals:** amoxicillin (PubChem CID 33613), cloxacillin (PubChem CID 6098), erythromycin (PubChem CID 12560), penicillin (PubChem CID 2349), tetracycline (PubChem CID 54675776), vancomycin (PubChem CID 14969), T3 (PubChem CID 5920), T4 (PubChem CID 5819)
- **Diseases:** pneumonia (MONDO:0005249)

## Full-text entities

- **Diseases:** pneumonia (MESH:D011014), bacterial (MESH:D001424)
- **Chemicals:** amoxicillin (MESH:D000658), cloxacillin (MESH:D003023), Methicillin (MESH:D008712), erythromycin (MESH:D004917), iron (MESH:D007501), vancomycin (MESH:D014640), tetracycline (MESH:D013752), T3 (MESH:D014284), T4 (MESH:D013974), cortisol (MESH:D006854), penicillin (MESH:D010406)
- **Species:** Homo sapiens (human, species) [taxon 9606], Ovis aries (domestic sheep, species) [taxon 9940], Staphylococcus aureus (species) [taxon 1280]
- **Cell lines:** CLEC4E — Gallus gallus (Chicken), Spontaneously immortalized cell line (CVCL_JF73)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12197726/full.md

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Source: https://tomesphere.com/paper/PMC12197726