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The variable response of bacteria to free haemoglobin in the tissues
Abstract:
The local enhancement of infection by exogenous ferric iron, as ferric ammonium citrate, and by ferrous iron as guinea-pig haemoglobin, was assessed in studies with 55 strains of bacteria injected into the skin of guinea-pigs. The test organisms included Staphylococcus aureus, Streptococcus spp., Klebsiella spp., Escherichia coli and Pseudomonas aeruginosa. Four strains of Bacteroides spp. were tested with haemoglobin only. As previously reported with other strains, enhancement of infection by members of a given species by ferric iron was variable; in this study infection with only 11 of 59 strains was enhanced. Haemoglobin either of equal or lesser iron content was a more potent enhancer, affecting 27 of the 59 strains. The enhancement ranged from two-fold to 80-fold, the higher figures on the whole being characteristic of haemoglobin enhancement. Some few instances of depression by both haemoglobin and ferric ammonium citrate were noted. A few tests were made with systemic haemoglobin but the concentrations attainable were largely ineffective. Enhancement of infection did not appear to be related to the capacity of a strain to lyse or digest host red blood cells. In so far as guinea-pigs, whose antibacterial defences are lowered by ferric or ferrous iron, represent human subjects at risk of infection because of clinical circumstances characterised by excess of available iron--either exogenous or as a result of haemolysis--our results with organisms of a kind commonly associated with infection in hospitals suggest that only a small proportion of environmental bacteria can take advantage of any decreased resistance associated with iron excess.
Insights
Iron, in both ferric and ferrous forms, can enhance bacterial infections. However, hemoglobin was a more potent enhancer than ferric ammonium citrate, suggesting limited bacterial adaptation to iron excess.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Iron is essential for bacterial growth and virulence.
- Excess iron availability, from exogenous sources or hemolysis, may compromise host defenses.
- Understanding how iron influences bacterial infection is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of exogenous ferric iron and ferrous iron (as hemoglobin) in enhancing bacterial skin infections in guinea pigs.
- To compare the enhancing effects of ferric ammonium citrate and hemoglobin on bacterial infections.
- To determine if bacterial lysis of red blood cells correlates with iron-induced enhancement.
Main Methods:
- Infection models using guinea pig skin injected with various bacterial strains (Staphylococcus aureus, Streptococcus spp., Klebsiella spp., Escherichia coli, Pseudomonas aeruginosa, Bacteroides spp.).
- Administration of ferric ammonium citrate (exogenous ferric iron) and guinea pig hemoglobin (ferrous iron) to assess infection enhancement.
- Quantification of infection enhancement and comparison between iron sources.
- Evaluation of bacterial capacity to lyse red blood cells.
Main Results:
- Ferric iron (ferric ammonium citrate) enhanced infection in 11 out of 59 strains.
- Hemoglobin enhanced infection in 27 out of 59 strains, with enhancement ranging from two-fold to 80-fold.
- Hemoglobin was a more potent enhancer than ferric ammonium citrate.
- Some instances of infection depression were observed with both iron sources.
- Enhancement did not correlate with bacterial red blood cell lysis ability.
Conclusions:
- While iron excess can lower host antibacterial defenses, only a small proportion of common hospital-associated bacteria can exploit this increased iron availability to enhance infection.
- Hemoglobin is a more effective enhancer of bacterial infection than ferric ammonium citrate.
- The capacity of bacteria to lyse red blood cells is not linked to iron-mediated enhancement of infection.
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