Pertussis (whooping cough) is an acute, highly contagious respiratory infection caused by the bacterium Bordetella pertussis. After colonizing the ciliated respiratory epithelium, the organism elaborates virulence factors — chiefly pertussis toxin (an AB5 exotoxin that ADP-ribosylates the inhibitory G protein Gαi, driving unrestrained cAMP accumulation) acting in concert with adenylate cyclase toxin — that subvert host defenses and produce the characteristic paroxysmal coughing illness with inspiratory whoop and post-tussive emesis. Disease is most severe in unvaccinated young infants, who may develop apnea, cyanosis, and marked leukocytosis. It is vaccine-preventable (DTaP/Tdap), and macrolides are the conventional antibiotic, though macrolide resistance is emerging in some regions.
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name: Pertussis
creation_date: "2026-06-28T00:00:00Z"
description: >
Pertussis (whooping cough) is an acute, highly contagious respiratory infection
caused by the bacterium Bordetella pertussis. After colonizing the ciliated
respiratory epithelium, the organism elaborates virulence factors — chiefly
pertussis toxin (an AB5 exotoxin that ADP-ribosylates the inhibitory G protein
Gαi, driving unrestrained cAMP accumulation) acting in concert with adenylate
cyclase toxin — that subvert host defenses and produce the characteristic
paroxysmal coughing illness with inspiratory whoop and post-tussive emesis.
Disease is most severe in unvaccinated young infants, who may develop apnea,
cyanosis, and marked leukocytosis. It is vaccine-preventable (DTaP/Tdap), and
macrolides are the conventional antibiotic, though macrolide resistance is
emerging in some regions.
category: Infectious Disease
parents:
- Bacterial Respiratory Infection
synonyms:
- Whooping cough
- Bordetella pertussis infection
disease_term:
preferred_term: pertussis
term:
id: MONDO:0005077
label: pertussis
pathophysiology:
- name: Bordetella pertussis Respiratory Colonization
role: trigger
description: >
Bordetella pertussis colonizes the ciliated epithelium of the respiratory
tract and, through its virulence factors, subverts host immune defenses to
establish infection. This colonization is the proximal event from which both
toxin-mediated disease and the antibiotic-target biology follow.
cell_types:
- preferred_term: ciliated airway epithelial cell
term:
id: CL:0000064
label: ciliated cell
biological_processes:
- preferred_term: adhesion of symbiont to host
term:
id: GO:0044406
label: adhesion of symbiont to host
evidence:
- reference: PMID:41893571
supports: SUPPORT
evidence_source: OTHER
snippet: >-
PTx works in concert with the bacterium's adenylate cyclase toxin (ACT) to
subvert immune defenses and establish infection.
explanation: >-
Establishes that B. pertussis virulence factors subvert immune defenses to
establish respiratory infection. Evidence source is OTHER as this is a review
article.
downstream:
- target: Pertussis Toxin-Mediated Disruption of Host Gi Signaling
description: >-
The colonizing organism elaborates pertussis toxin, which disrupts host cell
signaling.
- target: Bacterial Ribosomal Translation (Macrolide Target)
description: >-
The organism's ribosome is the target of macrolide antibiotic therapy.
- name: Pertussis Toxin-Mediated Disruption of Host Gi Signaling
role: effector
description: >
Pertussis toxin, an AB5-type exotoxin, uses its enzymatic A subunit to
ADP-ribosylate the alpha-subunit of inhibitory G proteins (Gαi), preventing
receptor-induced inhibition of adenylyl cyclase and causing unrestrained cAMP
accumulation in host cells — a canonical mechanism underlying many pertussis
disease manifestations.
biological_processes:
- preferred_term: response to toxic substance
term:
id: GO:0009636
label: response to toxic substance
evidence:
- reference: PMID:41893571
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Pertussis toxin (PTx) is a major virulence factor of Bordetella pertussis
and an AB5-type exotoxin that disrupts host signaling.
explanation: >-
Identifies pertussis toxin as the major AB5 exotoxin virulence factor that
disrupts host signaling. Evidence source is OTHER as this is a review article.
- reference: PMID:41893571
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Its enzymatic A subunit ADP-ribosylates the α-subunit of inhibitory G
proteins (Gαi), preventing them from mediating receptor-induced inhibition of
adenylyl cyclase (AC). This leads to unrestrained cAMP accumulation in host
cells
explanation: >-
Details the molecular mechanism — ADP-ribosylation of Gαi causing
unrestrained cAMP accumulation. Evidence source is OTHER as this is a review
article.
downstream:
- target: Paroxysmal Coughing Illness
description: >-
Toxin-mediated disruption of host signaling produces the characteristic
paroxysmal coughing illness.
- name: Paroxysmal Coughing Illness
role: consequence
description: >
The clinical syndrome of pertussis is a paroxysmal coughing illness, classically
with an inspiratory whoop and post-tussive emesis. In young infants it may
manifest as cyanosis or facial flushing during coughing fits and apnea, and is
associated with marked leukocytosis.
biological_processes:
- preferred_term: inflammatory response
term:
id: GO:0006954
label: inflammatory response
modifier: INCREASED
locations:
- preferred_term: respiratory system
term:
id: UBERON:0001004
label: respiratory system
evidence:
- reference: PMID:41963827
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
presented with paroxysmal coughing
explanation: >-
Clinical cohort documenting paroxysmal coughing as the predominant
presentation of pertussis. Evidence source is HUMAN_CLINICAL as this is a
clinical cohort study.
downstream: []
- name: Bacterial Ribosomal Translation (Macrolide Target)
role: therapeutic_vulnerability
conforms_to: "bacterial_protein_synthesis_inhibition#Bacterial mRNA Translation by the Ribosome"
description: >
B. pertussis depends on its bacterial ribosome for protein synthesis.
Macrolides (e.g., azithromycin), the conventional antibiotics for pertussis,
bind the 50S ribosomal subunit and block bacterial protein synthesis — the
molecular target underlying antibiotic therapy (which reduces transmissibility
more than it alters the toxin-driven cough once established).
biological_processes:
- preferred_term: translation
term:
id: GO:0006412
label: translation
evidence:
- reference: PMID:24336183
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The ribosome is one of the main antibiotic targets in the bacterial cell.
explanation: >-
Establishes the bacterial ribosome as the target of macrolides and other
protein-synthesis inhibitors, the step this node represents. Evidence source
is OTHER as this is a review article.
downstream:
- target: Emerging Macrolide Resistance
description: >-
Macrolide resistance in B. pertussis erodes the efficacy of ribosome-targeting
therapy.
- name: Emerging Macrolide Resistance
role: adaptive_escape
conforms_to: "bacterial_protein_synthesis_inhibition#Ribosomal Target Resistance"
description: >
Macrolide-resistant B. pertussis is an emerging concern in some regions, which
can render azithromycin ineffective and shift treatment toward alternatives such
as trimethoprim-sulfamethoxazole.
biological_processes:
- preferred_term: response to antibiotic
term:
id: GO:0046677
label: response to antibiotic
evidence:
- reference: PMID:41963827
supports: SUPPORT
evidence_source: IN_VITRO
snippet: >-
high-level resistance to azithromycin but sensitivity to
trimethoprim-sulfamethoxazole, levofloxacin, doxycycline
explanation: >-
In vitro drug-susceptibility testing of B. pertussis isolates showing
high-level azithromycin resistance with retained sensitivity to alternatives.
Evidence source is IN_VITRO as this is an in vitro susceptibility assay of
isolates (in this cohort all 25 isolates were azithromycin-resistant,
grounding the "in some regions" caveat).
downstream: []
phenotypes:
- category: Respiratory
name: Whooping Cough
description: >
Paroxysmal coughing fits, classically followed by an inspiratory "whoop"; the
defining manifestation of pertussis.
phenotype_term:
preferred_term: Whooping cough
term:
id: HP:0031247
label: Whooping cough
evidence:
- reference: PMID:41963827
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
presented with paroxysmal coughing
explanation: >-
Most hospitalized cases presented with paroxysmal coughing. Evidence source
is HUMAN_CLINICAL as this is a clinical cohort study.
- category: Gastrointestinal
name: Post-tussive Vomiting
description: >
Vomiting after coughing paroxysms (post-tussive emesis), a characteristic
feature of pertussis.
phenotype_term:
preferred_term: Post-tussive vomiting
term:
id: HP:0002013
label: Vomiting
evidence:
- reference: PMID:41963827
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
post-tussive emesis
explanation: >-
Post-tussive emesis was documented in the clinical cohort. Evidence source is
HUMAN_CLINICAL as this is a clinical cohort study.
- category: Respiratory
name: Apnea
description: >
Apnea, particularly in young infants, is a dangerous manifestation of severe
pertussis.
phenotype_term:
preferred_term: Apnea
term:
id: HP:0002104
label: Apnea
evidence:
- reference: PMID:41963827
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
had apnea
explanation: >-
Apnea was documented among hospitalized pertussis cases. Evidence source is
HUMAN_CLINICAL as this is a clinical cohort study.
- category: Respiratory
name: Cyanosis
description: >
Cyanosis (or facial flushing) during coughing fits, especially in infants.
phenotype_term:
preferred_term: Cyanosis
term:
id: HP:0000961
label: Cyanosis
evidence:
- reference: PMID:41963827
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
manifested cyanosis or facial flushing during coughing
explanation: >-
Over half of hospitalized cases manifested cyanosis or facial flushing during
coughing. Evidence source is HUMAN_CLINICAL as this is a clinical cohort study.
- category: Hematologic
name: Leukocytosis
description: >
Marked leukocytosis (with lymphocyte predominance) is characteristic of
pertussis and elevated white cell count is a risk factor for severe disease.
phenotype_term:
preferred_term: Leukocytosis
term:
id: HP:0001974
label: Increased total leukocyte count
evidence:
- reference: PMID:41963827
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
elevated white blood cell count
explanation: >-
Elevated white blood cell count was an independent risk factor for severe
pertussis. Evidence source is HUMAN_CLINICAL as this is a clinical cohort
study.
- category: Constitutional
name: Fever
description: >
Low-grade fever may accompany pertussis, though it is often absent.
phenotype_term:
preferred_term: Fever
term:
id: HP:0001945
label: Fever
treatments:
- name: Azithromycin
description: >
Macrolide antibiotic that binds the 50S bacterial ribosome and inhibits protein
synthesis; the conventional antibiotic for pertussis, primarily reducing
transmissibility. Emerging macrolide-resistant B. pertussis in some regions can
necessitate alternatives such as trimethoprim-sulfamethoxazole.
therapeutic_modality: SMALL_MOLECULE
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: azithromycin
term:
id: CHEBI:2955
label: azithromycin
target_mechanisms:
- target: Bacterial Ribosomal Translation (Macrolide Target)
treatment_effect: INHIBITS
description: >-
Azithromycin binds the 50S ribosome and arrests B. pertussis protein
synthesis, clearing carriage and reducing transmission.
- name: Pertussis Vaccination
description: >
Acellular pertussis vaccination (DTaP in infants/children, Tdap boosters
including maternal immunization) is the key strategy for preventing severe
pertussis, particularly in young infants.
treatment_term:
preferred_term: vaccination
term:
id: MAXO:0001017
label: vaccination
evidence:
- reference: PMID:41963827
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
timely completion of the primary pertussis vaccination series in infants
remains a key strategy for preventing severe pertussis
explanation: >-
The cohort concludes that timely primary pertussis vaccination is key to
preventing severe disease. Evidence source is HUMAN_CLINICAL as this is a
clinical cohort study.
notes: >
Created as part of the Respiratory Infections project (vaccine-preventable
bacterial respiratory infection). Conforms to the
bacterial_protein_synthesis_inhibition module (ribosomal macrolide target +
emerging resistance). Toxin-mediated pathogenesis (pertussis toxin / adenylate
cyclase toxin) is the core mechanism. The infectious_agent (NCBITaxon) block was
omitted at creation and Bordetella pertussis is described in the text.