Aeromonas Virulence and Iron
Literature Search Report

For: Aeromonas Bacteraemia in Haematological Malignancy (Journal of Infection) Mode: academic-paper lit-review · Fidelity spectrum · Medium oversight Generated: 2026-05-20 N = 11 sources

Search Strategy

Databases: PubMed/MEDLINE; Zotero personal library (keyword + semantic); forward citation tracking

Search strings:

(Aeromonas) AND (iron acquisition OR siderophore OR FeoB OR ferric uptake) — 5 hits [Title/Abstract] (Aeromonas) AND (siderophore OR amonabactin OR ferric iron) — 5 hits (Aeromonas) AND (iron overload OR deferoxamine OR thalassemia) — 1 hit Zotero keyword: "Aeromonas iron" — 12 items retrieved

Inclusion: Peer-reviewed; directly addresses iron acquisition mechanisms or iron-dependent host risk in Aeromonas; English; no date limit (foundational works included).

Initial: 35 candidates After title/abstract screen: 15 Final included: 11

Annotated Bibliography in Paper Format

Theme 1
Iron as an Essential Virulence Determinant — Gene Regulation and Iron-Responsive Phenotypes

Iron is not merely a nutrient for Aeromonas: it is a master signal that co-ordinates the expression of virulence factor networks. This relationship was conceptually established by Byers et al. (1991), who classified iron acquisition in motile aeromonads into two streams — siderophore-dependent (utilising amonabactin or enterobactin to strip ferric iron from host transferrin and lactoferrin) and siderophore-independent (direct acquisition from host haem-containing molecules). This classification remains the organisational backbone of Aeromonas iron biology.

Byers BR, Massad G, Barghouthi S, Arceneaux JE (1991). Iron acquisition and virulence in the motile aeromonads: siderophore-dependent and -independent systems. Experientia 47(5):416–8. PMID: 1828435
Type
Review / experimental
Key findings
Aeromonas isolates producing amonabactin acquire iron from both host transferrin (siderophore-dependent) and haem molecules (siderophore-independent). Isolates producing enterobactin instead do not utilise transferrin-iron and rely exclusively on haem-iron. Foundational dichotomy paper.
Relevance
Establishes that Aeromonas employs at least two mechanistically distinct iron acquisition pathways, consistent with adaptation to different iron-availability niches within a host.
Quality
High Seminal; frequently cited; methodology pre-genomic but conceptually sound.
Use in paper
Introduction / Discussion (iron-virulence axis framing)

The genomic ubiquity of iron-regulated genes across Aeromonas was confirmed by Dubey et al. (2022), who performed whole-genome sequencing on Aeromonas media strain SD/21-15 alongside 24 public-domain Aeromonas genomes spanning clinical and environmental sources. The ferric uptake regulator (fur), haem receptor genes, and siderophore biosynthesis/uptake loci were detected in all isolates examined, confirming iron acquisition as a core conserved feature of the genus rather than a strain-specific virulence determinant.

Dubey S, Ager-Wick E, Peng B, Evensen Ø, Sørum H, Munang'andu HM (2022). Characterisation of virulence and antimicrobial resistance genes of Aeromonas media strain SD/21-15 from marine sediments. Frontiers in Microbiology 13:1022639. DOI: 10.3389/fmicb.2022.1022639
Type
Genomics / comparative genomics
Key findings
Fur, heme receptor genes, and siderophore genes present in all 25 Aeromonas genomes analysed. T2SS conserved; T6SS variable. Plasmid-mediated transfer of virulence and AMR genes demonstrated.
Relevance
Supports the proposition that iron acquisition is genus-wide, not species-restricted — relevant to multi-species cohort in the manuscript.
Quality
High Multi-genome; open-access.
Use in paper
Introduction (genomic basis of iron dependence)

Under conditions of iron limitation — mimicking the hypoferraemic host environment — A. hydrophila responds with a co-ordinated transcriptional and translational programme. Teng et al. (2018) used RNA-seq and iTRAQ proteomics to characterise the full response to iron chelation with 2,2′-dipyridyl. Of 1,204 differentially expressed genes, the most enriched functional categories were iron transport, siderophore biosynthesis (enterobactin pathway genes prominently), and virulence effectors. Phenotypically, protease activity, haemolytic activity, lipase activity, and swimming motility were all increased under iron-limiting conditions, and experimental fish infection caused higher mortality when bacteria were pre-cultured under iron restriction. The study confirms that iron limitation does not suppress Aeromonas virulence — it amplifies it.

Teng T, Xi B, Chen K, Pan L, Xie J, Xu P (2018). Comparative transcriptomic and proteomic analyses reveal upregulated expression of virulence and iron transport factors of Aeromonas hydrophila under iron limitation. BMC Microbiology 18:52. DOI: 10.1186/s12866-018-1178-8
Type
Experimental — multi-omics (RNA-seq + iTRAQ)
Key findings
1,204 DEGs and 236 DEPs under iron limitation; enrichment for iron transport, enterobactin synthesis, and virulence processes. All four virulence phenotypes (protease, haemolysin, lipase, motility) enhanced. Higher fish mortality after iron-limited culture.
Relevance
Mechanistic evidence that the iron-depleted host milieu — including haematological malignancy (anemia of inflammation, iron sequestration by IL-6/hepcidin) — paradoxically triggers Aeromonas virulence gene upregulation.
Quality
High Two independent omics platforms with qPCR validation; aquaculture A. hydrophila (limits direct human-pathogen extrapolation).
Use in paper
Discussion (mechanistic basis of host iron restriction → enhanced bacterial virulence)

A parallel proteomics study by Lange et al. (2020) specifically examined the response of virulent A. hydrophila to deferoxamine mesylate (DFO) — the xenosiderophore widely used clinically as an iron chelator in transfusion-dependent patients. Virulent A. hydrophila cultured in DFO-supplemented media showed differential upregulation of proteins grouped by gene ontology into iron ion transport, siderophore transport, and siderophore uptake transport, forming predicted protein–protein interaction networks. Notably, upregulation was detectable at the protein level even when differential gene expression at the mRNA level was unremarkable, suggesting post-transcriptional regulation of iron acquisition during DFO exposure.

Lange MD, Abernathy J, Shoemaker CA, Zhang D, Kirby A, Peatman E, Beck BH (2020). Proteome analysis of virulent Aeromonas hydrophila reveals the upregulation of iron acquisition systems in the presence of a xenosiderophore. FEMS Microbiology Letters 367(20):fnaa169. DOI: 10.1093/femsle/fnaa169
Type
Experimental — comparative proteomics (DFO vs. control media)
Key findings
DFO exposure upregulates iron acquisition protein networks; post-transcriptional regulation implied; increased virulence in catfish challenge model with DFO-cultured bacteria.
Relevance
Directly addresses deferoxamine — the chelation agent used in iron-overloaded thalassaemia and HSCT patients — as a potential promoter of Aeromonas virulence.
Quality
Med-High Aquaculture context; human clinical extrapolation requires caution.
Use in paper
Discussion (deferoxamine as host-side risk amplifier)

Theme 2
Siderophore Systems — Amonabactin, Enterobactin, and Xenosiderophore Exploitation

The predominant Aeromonas siderophore in clinical mesophilic isolates is amonabactin, a catecholate-hydroxamate hybrid that acquires ferric iron from the host iron-binding proteins transferrin and lactoferrin with high efficiency. Stintzi & Raymond (2000) provided the first direct kinetic determination of iron removal from the three molecular forms of ferric transferrin (diferric, N-terminal monoferric, C-terminal monoferric) by amonabactin. Key finding: amonabactin removes iron from C-terminal monoferric transferrin but not from N-terminal monoferric transferrin; paradoxically, iron removal from both sites is more rapid in diferric transferrin than in either monoferric form, implying allosteric co-ordination between the lobes. Growth promotion was independent of iron saturation status (30–100%), confirming a diffusible siderophore mechanism rather than direct contact.

Stintzi A, Raymond KN (2000). Amonabactin-mediated iron acquisition from transferrin and lactoferrin by Aeromonas hydrophila: direct measurement of individual microscopic rate constants. Journal of Biological Inorganic Chemistry 5(1):57–66. DOI: 10.1007/pl00010655
Type
Experimental biochemistry — kinetics
Key findings
Amonabactin removes iron from diferric transferrin at both sites; cannot remove from N-terminal monoferric alone; growth promotion independent of protein iron saturation (30–100%). Siderophore is diffusible.
Relevance
Establishes amonabactin as an efficient extractor of host transferrin-iron — relevant to saturated-transferrin states (iron overload) where transferrin-bound iron is readily stripped.
Quality
High Rigorous kinetics; single species/strain.
Use in paper
Introduction / Discussion (siderophore mechanism)

Beyond amonabactin, A. hydrophila ATCC 7966T harbours an outer membrane receptor for exogenously supplied enterobactin (the predominant E. coli siderophore), designated IrgA. Funahashi et al. (2013) characterised IrgA by transposon mutagenesis and complementation, demonstrating iron-regulated expression (Fur-box in promoter) and TonB2-dependent energisation. This capacity for xenosiderophore utilisation has direct clinical relevance: in polymicrobial infections or the gut microbiome context of neutropenic patients, Aeromonas can exploit siderophores produced by co-colonising Enterobacteriaceae without expending biosynthetic energy.

Funahashi T, Tanabe T, Miyamoto K, Tsujibo H, Maki J, Yamamoto S (2013). Characterisation of a gene encoding the outer membrane receptor for ferric enterobactin in Aeromonas hydrophila ATCC 7966(T). Bioscience, Biotechnology, and Biochemistry 77(2):353–60. DOI: 10.1271/bbb.120774
Type
Experimental — microbiology / genetics
Key findings
IrgA is the outer membrane receptor for ferric enterobactin; iron-regulated (Fur); TonB2-dependent; enables A. hydrophila to exploit enterobactin from co-colonising Enterobacteriaceae.
Relevance
Xenosiderophore exploitation extends Aeromonas iron acquisition repertoire in polymicrobial clinical settings (22% of this cohort).
Quality
High Genetic characterisation with complementation.
Use in paper
Discussion (polymicrobial bacteraemia iron ecology)

The same group subsequently characterised a second xenosiderophore receptor, DesA, specific for ferrioxamine B — the ferric form of deferoxamine (DFO). Funahashi et al. (2014) demonstrated that A. hydrophila can use DFO as an iron source by importing ferric-DFO via DesA, an AraC-type regulator-controlled outer membrane protein energised by TonB2. This mechanistically explains the observed clinical association between DFO therapy and Aeromonas infection: DFO, administered to chelate and excrete excess host iron, paradoxically provides Aeromonas with a pre-loaded iron-delivery vehicle.

Funahashi T, Tanabe T, Maki J, Miyamoto K, Tsujibo H, Yamamoto S (2014). Identification and characterisation of Aeromonas hydrophila genes encoding the outer membrane receptor of ferrioxamine B and an AraC-type transcriptional regulator. Bioscience, Biotechnology, and Biochemistry 78(10):1777–87. DOI: 10.1080/09168451.2014.932669
Type
Experimental — microbiology / genetics
Key findings
DesA receptor imports ferric-DFO (ferrioxamine B); regulated by AraC-type regulator DesR under iron limitation; TonB2-dependent. DFO acts as a xenosiderophore that Aeromonas exploits for iron.
Relevance
Direct mechanistic explanation for the deferoxamine–Aeromonas clinical risk (see Chompoonuch 2009). DFO = iron delivery to bacteria in iron-overloaded patients.
Quality
High Genetic characterisation with complementation; A. hydrophila ATCC reference strain.
Use in paper
Discussion (mechanistic basis of DFO risk)

Beyond catecholate/hydroxamate siderophores, Aeromonas also possesses haem-acquisition systems. Maltz et al. (2015) used a transposon mutagenesis screen in A. veronii to characterise two parallel systems: a siderophore utilisation pathway (disrupted by viuB insertion) and an outer membrane haem receptor (hgpB) with a cognate transcriptional activator (hgpR). The hgpB mutant was markedly impaired in colonising the medicinal leech gut — an iron-rich environment. Across 36 Aeromonas genome sequences queried, haem utilisation genes were far more broadly distributed than siderophore genes, suggesting haem-iron acquisition is the more ancestral and conserved pathway.

Maltz M, LeVarge BL, Graf J (2015). Identification of iron and heme utilisation genes in Aeromonas and their role in colonisation of the leech digestive tract. Frontiers in Microbiology 6:763. DOI: 10.3389/fmicb.2015.00763
Type
Experimental — mutagenesis, in vivo colonisation
Key findings
viuB (siderophore) and hgpB (haem receptor) both required for growth in blood under iron limitation; hgpB more broadly conserved across 36 Aeromonas genomes; haem-iron acquisition critical for in vivo gut colonisation.
Relevance
Haem-iron acquisition (from haemolysis or mucosal sources) is likely operative in Aeromonas bacteraemia, particularly in haematological patients with red cell lysis or transfusion-related haem exposure. A. veronii strain directly relevant (44.4% of NCKUH cohort).
Quality
High Both in vitro and in vivo data.
Use in paper
Discussion (haem-iron acquisition as virulence mechanism in haematological malignancy)

Theme 3
Siderophore-Independent Fe²⁺ Acquisition — The Feo System as a Master Virulence Regulator

While siderophore-mediated ferric (Fe³⁺) iron acquisition has been extensively characterised, Aeromonas also possesses a direct ferrous (Fe²⁺) uptake system — the Feo system — adapted to the reducing microenvironments of abscesses, anaerobic gut segments, and iron-overloaded extracellular fluid. Guan et al. (2025) generated a stable ΔfeoB mutant in A. veronii TH0426 and characterised its phenotype comprehensively. Loss of FeoB (the transmembrane NTPase catalysing Fe²⁺ import) impaired growth under iron-limiting conditions, reduced motility, adhesion, invasion, and cytotoxicity, and caused a 178-fold elevation in LD₅₀ relative to wild-type — the largest single-gene virulence attenuation reported in this species. Antioxidant capacity was also diminished, consistent with iron's dual role in superoxide dismutase and catalase function. Complementation with wild-type feoB restored all phenotypes. This study positions FeoB-mediated Fe²⁺ acquisition as a master virulence regulator integrating iron nutrition with motility, adhesion, and oxidative stress resistance.

Guan YC, Liang S, Wang YD, Bai SY, Huang CB, Gong JZ, Shi WQ, Kang YH, Shan XF, Huang SY (2025). The ferrous iron transporter FeoB mediates motility, biofilm formation, and virulence in Aeromonas veronii. Microbial Pathogenesis 208:108014. DOI: 10.1016/j.micpath.2025.108014
Type
Experimental — genetic knockout, in vitro / in vivo
Key findings
ΔfeoB: 178-fold LD₅₀ attenuation; impaired motility, adhesion, invasion, cytotoxicity (2.62-fold lower vs. wild-type), antioxidant capacity; all complemented by feoB reintroduction. Growth under iron-limited conditions impaired.
Relevance
NTBI-rich iron-overload environment of transfusion-dependent haematological patients may specifically fuel FeoB-dependent virulence. A. veronii is the dominant species in the NCKUH cohort (44.4%).
Quality
High Comprehensive mutant phenotyping; in vivo Carassius model; 2025 publication.
Use in paper
Discussion (Fe²⁺/Feo system activated by iron overload)

Theme 4
Host Iron Overload — Pathophysiology and Clinical Risk

The mechanistic framework linking host iron overload to bacterial pathogenicity was synthesised by Ganz (2018) in a foundational review of nutritional immunity. The central premise is that iron-targeted host defences — mucosal sequestration (lactoferrin, lipocalin-2/siderocalin), plasma hypoferraemia (IL-6 → hepcidin → ferroportin degradation), and phagosomal depletion (Nramp1) — are eroded in iron-overload states. When transferrin saturation approaches 100%, non-transferrin-bound iron (NTBI) accumulates in the extracellular milieu, providing a readily accessible iron pool for siderophilic bacteria including Vibrio vulnificus, Yersinia enterocolitica, Klebsiella pneumoniae, and Aeromonas spp. Clinical sources of iron overload directly relevant to haematological malignancy include chronic transfusion dependency (each unit of packed red cells adds ∼1 mg/mL iron), conditioning-related hepatic damage impairing hepcidin synthesis, and ineffective erythropoiesis suppressing hepcidin via erythroferrone.

Ganz T (2018). Iron and infection. International Journal of Hematology 107(1):7–15. DOI: 10.1007/s12185-017-2366-2
Type
Review (authoritative; Tomas Ganz, UCLA)
Key findings
NTBI (not transferrin-bound iron) is the specific species driving siderophilic bacterial growth; hypoferraemia of inflammation is lost in hepcidin-knockout mice; hepcidin analogue PR-73 rescues iron-overloaded mice from V. vulnificus sepsis.
Relevance
Mechanistic underpinning for iron overload as a host risk factor for Aeromonas bacteraemia; directly supports the 69.2% iron-overload prevalence finding in the NCKUH cohort.
Quality
High
Use in paper
Introduction / Discussion (host-side mechanism)

The clinical consequence of DFO-mediated iron delivery to Aeromonas was illustrated by Chompoonuch et al. (2009) in a case report of a 47-year-old woman with end-stage renal disease on haemodialysis who developed A. hydrophila bacteraemia with septic embolism and rhabdomyolysis while receiving deferoxamine for transfusion-related iron overload. The authors proposed that DFO provided Aeromonas with an iron source via the ferrioxamine B receptor mechanism — a hypothesis now mechanistically supported by Funahashi et al. (2014). The patient survived with aggressive renal replacement therapy. Although a single case report, this is one of the few published descriptions explicitly linking deferoxamine therapy and Aeromonas infection in a patient without underlying liver disease.

Chompoonuch S, Wangsomboonsiri W, Wongprasit P, Sungkanuparph S, Phakdeekitcharoen B (2009). Aeromonas hydrophila sepsis with septic embolism and rhabdomyolysis in a chronic iron overload haemodialysis patient treated with deferoxamine. NDT Plus 2(4):303–5. DOI: 10.1093/ndtplus/sfp029
Type
Case report
Key findings
A. hydrophila bacteraemia in a DFO-treated, iron-overloaded dialysis patient; rhabdomyolysis present; patient survived. Authors hypothesise DFO as iron source for Aeromonas.
Relevance
Clinical proof-of-concept for DFO–Aeromonas risk; rhabdomyolysis is a recognised complication of Aeromonas myonecrosis.
Quality
Low Single case report; limited evidence level; no mechanistic data.
Use in paper
Discussion (clinical illustration of DFO risk)

A broader epidemiological perspective on infection risk in iron-overloaded patients is provided by Wanachiwanawin (2000), reviewing infections in E-β thalassaemia. Among the spectrum of severe infections in this population — predominantly E. coli, Klebsiella, and Salmonella — Aeromonas is explicitly listed as a causative organism, particularly in splenectomised patients and those on DFO therapy. The review identifies iron overload, splenectomy, and granulocyte dysfunction as the three principal predisposing factors, with DFO therapy specifically linked to Yersinia enterocolitica but the same mechanism extending to Aeromonas.

Wanachiwanawin W (2000). Infections in E-beta thalassaemia. Journal of Pediatric Hematology/Oncology 22(6):581–7. DOI: 10.1097/00043426-200011000-00027
Type
Review
Key findings
Aeromonas among organisms causing severe infections in thalassaemia; DFO therapy classically associated with Yersinia but same mechanism applies; iron overload, splenectomy, and granulocyte dysfunction are principal risk factors.
Relevance
Establishes Aeromonas in the clinical spectrum of iron-overload infections in haematological patients; thalassaemia population shares transfusion burden and DFO exposure with haematological malignancy.
Quality
Medium Narrative review; thalassaemia population rather than haematological malignancy, but iron overload mechanism is shared.
Use in paper
Introduction (clinical background on iron overload and infection risk)

Literature Matrix

Source Fe²⁺ (Feo) Fe³⁺ / siderophore Xenosiderophore / DFO Haem-iron Host iron overload Clinical data Quality
Byers 1991 — ★ — ✓ — — High
Dubey 2022 — ✓ — ✓ — — High
Teng 2018 — ★ — — — — High
Lange 2020 — ★ ✓ — — — Med-High
Stintzi 2000 — ★ — — — — High
Funahashi 2013 — ★ ✓ — — — High
Funahashi 2014 — — ★ — — — High
Maltz 2015 — ✓ — ★ — — High
Guan 2025 ★ — — — — — High
Ganz 2018 — — — — ★ — High
Chompoonuch 2009 — — ✓ — ✓ ✓ Low CR
Wanachiwanawin 2000 — — ✓ — ✓ ✓ Medium

★ = primary focus   ✓ = covered   CR = case report

Identified Research Gaps

Recommended Sources by Paper Section

Section Key sources
Introduction — iron overload as host risk Ganz 2018; Wanachiwanawin 2000
Introduction — iron as Aeromonas virulence determinant Byers 1991; Dubey 2022; Teng 2018
Discussion — mechanisms of iron acquisition Stintzi 2000; Funahashi 2013; Funahashi 2014; Maltz 2015; Guan 2025
Discussion — deferoxamine clinical risk Funahashi 2014; Lange 2020; Chompoonuch 2009
Discussion — study limitations (ferritin/NTBI gap) Ganz 2018 (NTBI concept); Gap #1 above