Role of Iron, Zinc, and Copper Homeostasis in Patients with Multidrug-Resistant Bacterial Infections

Authors

  • Lubna Khalid Farhan University of Fallujah - College of applied science, Department of applied Chemistry, Iraq - Al_ anbar

Keywords:

Multidrug-resistant bacterial infections, Nutritional immunity, Iron metabolism, Trace element homeostasis, Inflammatory biomarkers

Abstract

Background: Disruption of iron, zinc, and copper homeostasis may contribute to immune dysfunction, inflammation, and disease severity in multidrug-resistant bacterial infections. Aims of the study: This study aimed to evaluate iron, zinc, and copper homeostasis in multidrug-resistant bacterial infections and determine their associations with inflammatory biomarkers, hematological parameters, and clinical risk factors. Methodology: A case–control study was conducted at Al-Habbobi Teaching Hospital, Thi-Qar, Iraq, between June 2025 and March 2026, including 60 patients with multidrug-resistant (MDR) bacterial infections, 60 with non-MDR infections, and 30 healthy controls. MDR isolates were identified according to CLSI guidelines. Serum iron, ferritin, transferrin, TIBC, zinc, copper, CRP, IL-6, TNF-α, and hematological parameters were measured using standard laboratory methods. Statistical analyses included ANOVA, Pearson correlation, and multivariate logistic regression, with P < 0.05 considered statistically significant. Result: Patients with MDR bacterial infections showed significantly higher BMI, inflammatory markers, WBC counts, and prevalence of diabetes, prior antibiotic use, and hospitalization than other groups. Escherichia coli was the predominant isolate. MDR infections exhibited marked reductions in serum iron, transferrin, TIBC, and zinc, with increased ferritin, copper, and Cu/Zn ratio (all P<0.001). Trace element alterations correlated significantly with inflammatory biomarkers. Previous antibiotic use, elevated Cu/Zn ratio, ferritin, CRP, low zinc, hospitalization, and diabetes independently predicted MDR bacterial infections. Conclusions: Disturbances in iron, zinc, and copper homeostasis are strongly associated with multidrug-resistant bacterial infections and parallel systemic inflammation. The Cu/Zn ratio, ferritin, and zinc may serve as valuable complementary biomarkers for assessing infection severity and identifying patients at increased risk of MDR infections.

References

M. A. Salam et al., “Antimicrobial resistance: A growing serious threat for global public health,” Healthcare, vol. 11, no. 13, 2023.

D. van Duin and D. Paterson, “Multidrug-resistant bacteria in the community: Trends and lessons learned,” Infect. Dis. Clin. North Am., vol. 30, no. 2, p. 377, 2016.

A. Talebi Bezmin Abadi et al., “World Health Organization report: Current crisis of antibiotic resistance,” BioNanoScience, vol. 9, no. 4, pp. 778–788, 2019.

E.-K. Jo, “Interplay between host and pathogen: Immune defense and beyond,” Exp. Mol. Med., vol. 51, no. 12, pp. 1–3, 2019.

A. Thakur, H. Mikkelsen, and G. Jungersen, “Intracellular pathogens: Host immunity and microbial persistence strategies,” J. Immunol. Res., vol. 2019, Art. no. 1356540, 2019.

C. Li, Y. Li, and C. Ding, “The role of copper homeostasis at the host–pathogen axis: From bacteria to fungi,” Int. J. Mol. Sci., vol. 20, no. 1, Art. no. 175, 2019.

Y. Chen et al., “Iron metabolism and its contribution to cancer,” Int. J. Oncol., vol. 54, no. 4, pp. 1143–1154, 2019.

M. Y. Hsu et al., “Iron: An essential element of cancer metabolism,” Cells, vol. 9, no. 12, Art. no. 2591, 2020.

A. C. Ross, “Impact of chronic and acute inflammation on extra- and intracellular iron homeostasis,” Am. J. Clin. Nutr., vol. 106, suppl. 6, pp. 1581S–1587S, 2017.

D. Skrajnowska and B. Bobrowska-Korczak, “Role of zinc in immune system and anticancer defense mechanisms,” Nutrients, vol. 11, no. 10, Art. no. 2273, 2019.

A. Hassan et al., “Role of zinc in mucosal health and disease: A review of physiological, biochemical, and molecular processes,” Cureus, vol. 12, no. 5, 2020.

A. Angajala et al., “Diverse roles of mitochondria in immune responses: Novel insights into immunometabolism,” Front. Immunol., vol. 9, Art. no. 1605, 2018.

G. Morris et al., “Redox regulation of the immune response,” Cell. Mol. Immunol., vol. 19, no. 10, pp. 1079–1101, 2022.

H. Deng et al., “The dysregulation of inflammatory pathways triggered by copper exposure,” Biol. Trace Elem. Res., vol. 201, no. 2, pp. 539–548, 2023.

S. D. Bushman and E. P. Skaar, “The exploitation of nutrient metals by bacteria for survival and infection in the gut,” PLoS Pathog., vol. 21, no. 10, Art. no. e1013580, 2025.

A. J. Monteith and E. P. Skaar, “The impact of metal availability on immune function during infection,” Trends Endocrinol. Metab., vol. 32, no. 11, pp. 916–928, 2021.

T. Baral et al., “Probiotics supplementation in tuberculosis: A scoping review,” Scientifica, vol. 2025, no. 1, Art. no. 6926727, 2025.

N. R. Kumar et al., “Multidrug-resistant sepsis: A critical healthcare challenge,” Antibiotics, vol. 13, no. 1, Art. no. 46, 2024.

M. Marchetti et al., “Iron metabolism at the interface between host and pathogen: From nutritional immunity to antibacterial development,” Int. J. Mol. Sci., vol. 21, no. 6, Art. no. 2145, 2020.

H. Moro, “The iron-infection axis revisited: From mechanistic insights to therapeutic frontiers,” J. Infect. Chemother., Art. no. 102818, 2025.

Y. Liao et al., “Ferritin’s role in infectious diseases: Exploring pathogenic mechanisms and clinical implications,” New Microbes New Infect., vol. 65, Art. no. 101582, 2025.

T. Ganz, “Iron and infection,” Int. J. Hematol., vol. 107, no. 1, pp. 7–15, 2018.

N. Z. Gammoh and L. Rink, “Zinc in infection and inflammation,” Nutrients, vol. 9, no. 6, Art. no. 624, 2017.

S.-L. Liao et al., “Association between serum zinc and toll-like-receptor-related innate immunity and infectious diseases in well-nourished children with a low prevalence of zinc deficiency: A prospective cohort study,” Nutrients, vol. 14, no. 24, Art. no. 5395, 2022.

S. Deumić et al., “Investigating the effect of zinc salts on Escherichia coli and Enterococcus faecalis biofilm formation,” Appl. Sci., vol. 15, no. 15, Art. no. 8383, 2025.

M. C. Linder, “Ceruloplasmin and other copper-binding components of blood plasma and their functions: An update,” Metallomics, vol. 8, no. 9, pp. 887–905, 2016.

C. Péladeau and J. K. Sandhu, “Aberrant NLRP3 inflammasome activation ignites the fire of inflammation in neuromuscular diseases,” Int. J. Mol. Sci., vol. 22, no. 11, Art. no. 6068, 2021.

J.-B. Meng et al., “The correlation between whole-blood copper and zinc levels and the Cu/Zn ratio and sepsis-induced left ventricular systolic dysfunction in patients with septic shock: A single-center prospective observational study,” Int. J. Gen. Med., vol. 14, pp. 7219–7234, 2021.

Y. H. Lee et al., “Serum concentrations of trace elements zinc, copper, selenium, and manganese in critically ill patients,” Biol. Trace Elem. Res., vol. 188, no. 2, p. 316, 2018.

C. Camaschella, A. Nai, and L. Silvestri, “Iron metabolism and iron disorders revisited in the hepcidin era,” Haematologica, vol. 105, no. 2, p. 260, 2020.

G. Bahi et al., “Evaluation of the hematological and biochemical markers of iron metabolism in pulmonary multidrug-resistant tuberculosis,” J. Trop. Med. Health, 2018.

C. J. Pyle, “Impact of macrophage zinc metabolism on host defense against Mycobacterium tuberculosis,” Ph.D. dissertation, The Ohio State Univ., Columbus, OH, USA, 2016.

M. Wisniewska et al., “Copper-to-zinc ratio as a disease biomarker in neonates with early-onset congenital infections,” Nutrients, vol. 9, no. 4, Art. no. 343, 2017.

M. S. H. Akash et al., “Diabetes-associated infections: Development of antimicrobial resistance and possible treatment strategies,” Arch. Microbiol., vol. 202, no. 5, pp. 953–965, 2020.

A. Toniolo et al., “The diabetes pandemic and associated infections: Suggestions for clinical microbiology,” Rev. Med. Microbiol., vol. 30, no. 1, p. 1, 2018.

Downloads

Published

2026-07-16

How to Cite

Farhan, L. K. (2026). Role of Iron, Zinc, and Copper Homeostasis in Patients with Multidrug-Resistant Bacterial Infections. Central Asian Journal of Medical and Natural Science, 7(4), 66–75. Retrieved from https://cajmns.casjournal.org/index.php/CAJMNS/article/view/3348

Issue

Section

Articles