Porin A and α/β-hydrolase are necessary and sufficient for hemolysis induced by Bartonella bacilliformis

Alexander A Dichter1, Florian Winklmeier1, Diana Munteh1

  • 1Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt am Main, Germany.

Nature Communications
|November 28, 2025
PubMed

Insights

Two Bartonella bacilliformis proteins, porin A and α/β-hydrolase, are essential for causing hemolytic anemia in Carrion's disease. Understanding these virulence factors may lead to new anti-virulence therapies.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Molecular Biology

Background:

  • Carrion's disease, endemic to the Andes, is a fatal hemolytic anemia caused by Bartonella bacilliformis.
  • Bartonella bacilliformis is a challenging pathogen for genetic studies due to its slow growth and fastidious nature.

Purpose of the Study:

  • To identify the specific factors of Bartonella bacilliformis responsible for inducing hemolysis.
  • To elucidate the molecular mechanisms underlying the hemolytic activity of B. bacilliformis.

Main Methods:

  • Screening of a Tn5 transposon mutant library to identify hemolytic genes.
  • Markerless deletion mutagenesis to generate porin A and α/β-hydrolase deletion mutants.
  • In silico analysis, site-directed mutagenesis, and inhibitor screening to characterize protein function.

Main Results:

  • Porin A and α/β-hydrolase were identified as necessary and sufficient for B. bacilliformis-induced hemolysis.
  • The catalytic triad of α/β-hydrolase (Ser205, Asp267, His310) is crucial for its hemolytic activity.
  • Compound 48/80 was found to be a potent inhibitor of hemolysis in the micromolar range.

Conclusions:

  • Porin A and α/β-hydrolase are key virulence factors in Bartonella bacilliformis.
  • Targeting these factors or their activity could lead to novel anti-virulence strategies against Carrion's disease.
  • These findings are particularly relevant given the rising antibiotic resistance in B. bacilliformis.

Related Concept Videos

Structure of Porins01:21

Structure of Porins

Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
3.8K
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
4.5K
Multi-pass Transmembrane Proteins and β-barrels01:09

Multi-pass Transmembrane Proteins and β-barrels

In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as...
6.4K
Antimicrobial Proteins01:23

Antimicrobial Proteins

Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
12.9K