USMLE Step 1 Microbiology & Immunology 2025 — 55 Q&A High-
Yield Practice Verified
Series:
CrashCourses Professional Study Series
Author:
Dr Z. Moomba, MBChB, MRCPsych | BethelWellness Ltd
Exam Target:
USMLE Step 1
Year:
2025/2026
Format:
55 Questions with Verified Answers and Rationales
>
Author's Note:
This document is an original work produced for the CrashCourses Professional Study Series.
Clinical questions and professional scenarios were composed by Dr Z. Moomba based on current
exam objectives, published guidelines, and evidence-based sources (2024–2025). All patient
names, ages, and case details are fictional. Any resemblance to existing published Q&A banks is
coincidental. For personal study use only — not for reproduction or redistribution.
SECTION A — FOUNDATIONS
Question 1
A 24-year-old woman presents to the emergency department with a sudden onset of high fever,
vomiting, and a diffuse, erythematous, macular rash resembling a sunburn. She is hypotensive.
Blood cultures are drawn. The suspected organism produces a toxin that binds directly to the MHC
II receptor and the T-cell receptor outside the antigen-binding site. Which of the following is the
most likely responsible virulence factor?
A) Protein A
B) Toxic shock syndrome toxin-1 (TSST-1)
C) M protein
,D) Shiga-like toxin
Answer: B
Rationale:
a) TSST-1 is a superantigen produced by Staphylococcus aureus that non-specifically cross-links
MHC II on macrophages to the variable region of the beta chain of T-cell receptors, causing a
massive release of cytokines (IFN-gamma, IL-1, IL-2).
b) The clinical picture of sudden fever, hypotension, and a sunburn-like rash points to Toxic Shock
Syndrome.
c) Protein A is an S. aureus virulence factor, but it binds the Fc portion of IgG to prevent
phagocytosis, rather than acting as a superantigen.
d) Staphylococcus aureus is the most common cause of osteomyelitis and acute endocarditis on
native, damaged valves. [First Aid 2024/2025]
Question 2
A 9-year-old boy is brought to the clinic due to involuntary, irregular, and non-rhythmic
movements of his limbs. His mother mentions he had a severe sore throat three weeks ago that
resolved without treatment. On examination, a new holosystolic murmur is heard at the apex. The
organism responsible for the antecedent infection possesses a key virulence factor that shares
structural homology with human cardiac tissue. What is this factor?
A) Coagulase
B) IgA protease
C) M protein
D) Tetano-spasmin
Answer: C
Rationale:
a) Streptococcus pyogenes (Group A Strep) produces M protein, which inhibits phagocytosis and
shares molecular mimicry with human cardiac myosin, leading to rheumatic fever.
b) Sydenham chorea and a new mitral regurgitation murmur following an untreated sore throat are
classic for acute rheumatic fever.
c) Coagulase is found in S. aureus, not S. pyogenes, and promotes clot formation to wall off the
bacteria.
d) Elevated ASO (anti-streptolysin O) titres confirm recent Group A Strep infection and risk of
post-strep sequelae. [CDC Guidelines 2025]
,Question 3
A 65-year-old man with a history of splenectomy following motor vehicle trauma presents with
sudden onset chills, high fever, and shortness of breath. Sputum Gram stain reveals Gram-
positive, lancet-shaped diplococci. A capsular swelling test is positive. Which of the following
describes the most likely pathogen?
A) Optochin resistant
B) Bacitracin sensitive
C) Optochin sensitive
D) Novobiocin resistant
Answer: C
Rationale:
a) Streptococcus pneumoniae is an alpha-hemolytic, optochin-sensitive, bile-soluble, Gram-
positive diplococcus with a prominent polysaccharide capsule.
b) The positive quellung reaction (capsular swelling) and the patient's asplenia (high risk for
encapsulated organisms — OPSI) point directly to S. pneumoniae.
c) Optochin resistance is characteristic of Streptococcus mutans and Streptococcus mitis
(Viridans group), not S. pneumoniae.
d) Asplenic patients require vaccination against pneumococcus, meningococcus, and
Haemophilus influenzae type B to prevent Overwhelming Post-Splenectomy Infection (OPSI).
[NHS Immunisation Green Book 2025]
Question 4
A 32-year-old woman is evaluated for burning on urination, increased frequency, and suprapubic
pain. Urinalysis shows positive nitrites and leukocyte esterase. Urine culture grows a Gram-
negative rod that ferments lactose. What is the most likely primary virulence factor mediating this
patient's condition?
A) P fimbriae
B) Urease
C) Lipid A
D) Polysaccharide capsule
Answer: A
, Rationale:
a) Uropathogenic Escherichia coli (UPEC) utilizes P fimbriae (pili) to adhere to uroepithelium,
preventing the bacteria from being washed away by urine flow.
b) The presentation of uncomplicated cystitis with lactose-fermenting, nitrite-positive Gram-
negative rods is classic for E. coli, the most common cause of UTI.
c) Lipid A is the toxic component of lipopolysaccharide (LPS) that causes septic shock, but it is not
the primary factor mediating initial uroepithelial adhesion.
d) Enterohaemorrhagic E. coli (EHEC O157:H7) causes HUS via Shiga toxin; importantly, antibiotics
are contraindicated in EHEC as they increase toxin release. [NICE NG109]
Question 5
A 45-year-old man undergoes an upper gastrointestinal endoscopy for chronic dyspepsia. A
biopsy is taken from the gastric antrum, which quickly turns a urea-containing medium pink. The
organism identified possesses a virulence factor that significantly increases the risk of gastric
adenocarcinoma. Which of the following is the treatment of choice?
A) Amoxicillin monotherapy
B) Metronidazole and ciprofloxacin
C) Omeprazole, clarithromycin, and amoxicillin
D) Bismuth subsalicylate alone
Answer: C
Rationale:
a) Helicobacter pylori is treated with triple therapy consisting of a proton pump inhibitor (e.g.,
omeprazole), clarithromycin, and amoxicillin (or metronidazole if penicillin-allergic).
b) The rapid urease test turning pink indicates the presence of H. pylori, an organism that uses
urease to neutralize gastric acid.
c) Amoxicillin monotherapy is insufficient and leads to rapid antimicrobial resistance; combination
therapy is essential.
d) The CagA (cytotoxin-associated gene A) protein is a major virulence factor of H. pylori strongly
associated with the development of gastric cancer. [ACG Clinical Guideline 2024]
Question 6
An 18-year-old college student presents to the student health center with a stiff neck,
photophobia, and a petechial rash on his lower extremities. Lumbar puncture reveals a high
Yield Practice Verified
Series:
CrashCourses Professional Study Series
Author:
Dr Z. Moomba, MBChB, MRCPsych | BethelWellness Ltd
Exam Target:
USMLE Step 1
Year:
2025/2026
Format:
55 Questions with Verified Answers and Rationales
>
Author's Note:
This document is an original work produced for the CrashCourses Professional Study Series.
Clinical questions and professional scenarios were composed by Dr Z. Moomba based on current
exam objectives, published guidelines, and evidence-based sources (2024–2025). All patient
names, ages, and case details are fictional. Any resemblance to existing published Q&A banks is
coincidental. For personal study use only — not for reproduction or redistribution.
SECTION A — FOUNDATIONS
Question 1
A 24-year-old woman presents to the emergency department with a sudden onset of high fever,
vomiting, and a diffuse, erythematous, macular rash resembling a sunburn. She is hypotensive.
Blood cultures are drawn. The suspected organism produces a toxin that binds directly to the MHC
II receptor and the T-cell receptor outside the antigen-binding site. Which of the following is the
most likely responsible virulence factor?
A) Protein A
B) Toxic shock syndrome toxin-1 (TSST-1)
C) M protein
,D) Shiga-like toxin
Answer: B
Rationale:
a) TSST-1 is a superantigen produced by Staphylococcus aureus that non-specifically cross-links
MHC II on macrophages to the variable region of the beta chain of T-cell receptors, causing a
massive release of cytokines (IFN-gamma, IL-1, IL-2).
b) The clinical picture of sudden fever, hypotension, and a sunburn-like rash points to Toxic Shock
Syndrome.
c) Protein A is an S. aureus virulence factor, but it binds the Fc portion of IgG to prevent
phagocytosis, rather than acting as a superantigen.
d) Staphylococcus aureus is the most common cause of osteomyelitis and acute endocarditis on
native, damaged valves. [First Aid 2024/2025]
Question 2
A 9-year-old boy is brought to the clinic due to involuntary, irregular, and non-rhythmic
movements of his limbs. His mother mentions he had a severe sore throat three weeks ago that
resolved without treatment. On examination, a new holosystolic murmur is heard at the apex. The
organism responsible for the antecedent infection possesses a key virulence factor that shares
structural homology with human cardiac tissue. What is this factor?
A) Coagulase
B) IgA protease
C) M protein
D) Tetano-spasmin
Answer: C
Rationale:
a) Streptococcus pyogenes (Group A Strep) produces M protein, which inhibits phagocytosis and
shares molecular mimicry with human cardiac myosin, leading to rheumatic fever.
b) Sydenham chorea and a new mitral regurgitation murmur following an untreated sore throat are
classic for acute rheumatic fever.
c) Coagulase is found in S. aureus, not S. pyogenes, and promotes clot formation to wall off the
bacteria.
d) Elevated ASO (anti-streptolysin O) titres confirm recent Group A Strep infection and risk of
post-strep sequelae. [CDC Guidelines 2025]
,Question 3
A 65-year-old man with a history of splenectomy following motor vehicle trauma presents with
sudden onset chills, high fever, and shortness of breath. Sputum Gram stain reveals Gram-
positive, lancet-shaped diplococci. A capsular swelling test is positive. Which of the following
describes the most likely pathogen?
A) Optochin resistant
B) Bacitracin sensitive
C) Optochin sensitive
D) Novobiocin resistant
Answer: C
Rationale:
a) Streptococcus pneumoniae is an alpha-hemolytic, optochin-sensitive, bile-soluble, Gram-
positive diplococcus with a prominent polysaccharide capsule.
b) The positive quellung reaction (capsular swelling) and the patient's asplenia (high risk for
encapsulated organisms — OPSI) point directly to S. pneumoniae.
c) Optochin resistance is characteristic of Streptococcus mutans and Streptococcus mitis
(Viridans group), not S. pneumoniae.
d) Asplenic patients require vaccination against pneumococcus, meningococcus, and
Haemophilus influenzae type B to prevent Overwhelming Post-Splenectomy Infection (OPSI).
[NHS Immunisation Green Book 2025]
Question 4
A 32-year-old woman is evaluated for burning on urination, increased frequency, and suprapubic
pain. Urinalysis shows positive nitrites and leukocyte esterase. Urine culture grows a Gram-
negative rod that ferments lactose. What is the most likely primary virulence factor mediating this
patient's condition?
A) P fimbriae
B) Urease
C) Lipid A
D) Polysaccharide capsule
Answer: A
, Rationale:
a) Uropathogenic Escherichia coli (UPEC) utilizes P fimbriae (pili) to adhere to uroepithelium,
preventing the bacteria from being washed away by urine flow.
b) The presentation of uncomplicated cystitis with lactose-fermenting, nitrite-positive Gram-
negative rods is classic for E. coli, the most common cause of UTI.
c) Lipid A is the toxic component of lipopolysaccharide (LPS) that causes septic shock, but it is not
the primary factor mediating initial uroepithelial adhesion.
d) Enterohaemorrhagic E. coli (EHEC O157:H7) causes HUS via Shiga toxin; importantly, antibiotics
are contraindicated in EHEC as they increase toxin release. [NICE NG109]
Question 5
A 45-year-old man undergoes an upper gastrointestinal endoscopy for chronic dyspepsia. A
biopsy is taken from the gastric antrum, which quickly turns a urea-containing medium pink. The
organism identified possesses a virulence factor that significantly increases the risk of gastric
adenocarcinoma. Which of the following is the treatment of choice?
A) Amoxicillin monotherapy
B) Metronidazole and ciprofloxacin
C) Omeprazole, clarithromycin, and amoxicillin
D) Bismuth subsalicylate alone
Answer: C
Rationale:
a) Helicobacter pylori is treated with triple therapy consisting of a proton pump inhibitor (e.g.,
omeprazole), clarithromycin, and amoxicillin (or metronidazole if penicillin-allergic).
b) The rapid urease test turning pink indicates the presence of H. pylori, an organism that uses
urease to neutralize gastric acid.
c) Amoxicillin monotherapy is insufficient and leads to rapid antimicrobial resistance; combination
therapy is essential.
d) The CagA (cytotoxin-associated gene A) protein is a major virulence factor of H. pylori strongly
associated with the development of gastric cancer. [ACG Clinical Guideline 2024]
Question 6
An 18-year-old college student presents to the student health center with a stiff neck,
photophobia, and a petechial rash on his lower extremities. Lumbar puncture reveals a high
