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Bacteriology Overview

35 min read

Introduction #

Bacteria are prokaryotic microorganisms that play crucial roles in human health and disease. Understanding bacterial structure, physiology, genetics, and pathogenesis is fundamental to medical microbiology and clinical practice[1,2]. This review provides a comprehensive overview of high-yield bacteriology concepts essential for USMLE Step 1 preparation.

Bacterial Structure and Classification #

Prokaryotic Cell Structure

Bacteria are single-celled prokaryotic organisms characterized by the absence of a membrane-bound nucleus and membrane-bound organelles[3]. The bacterial genome consists of a single circular chromosome located in the nucleoid region, along with extrachromosomal plasmids that often carry genes for antibiotic resistance and virulence factors[4].

The bacterial cell envelope varies significantly among species and serves as the primary basis for classification. The peptidoglycan cell wall, composed of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) cross-linked by peptide chains, provides structural integrity and determines cell shape[5]. This structure is the target of β-lactam antibiotics, which inhibit peptidoglycan synthesis by binding to penicillin-binding proteins[6].

Gram Staining and Cell Wall Architecture

The Gram stain, developed by Hans Christian Gram in 1884, remains the most fundamental classification method in bacteriology[7]. Gram-positive bacteria possess a thick peptidoglycan layer (20-80 nm) that retains crystal violet dye, appearing purple under microscopy[8]. This thick peptidoglycan contains teichoic acids and lipoteichoic acids, which contribute to cell wall rigidity and serve as virulence factors by promoting adherence to host tissues[9].

Gram-negative bacteria have a thin peptidoglycan layer (2-3 nm) surrounded by an outer membrane containing lipopolysaccharide (LPS)[10]. The LPS consists of three components: lipid A (endotoxin), core polysaccharide, and O-antigen[11]. Lipid A is a potent activator of the innate immune system, triggering release of pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 through Toll-like receptor 4 (TLR4) signaling[12]. This can lead to septic shock, characterized by fever, hypotension, disseminated intravascular coagulation, and multiorgan failure[13].

The periplasmic space between the inner and outer membranes of Gram-negative bacteria contains enzymes, including β-lactamases that confer antibiotic resistance[14]. Porins in the outer membrane allow selective passage of nutrients and antibiotics, with alterations in porin expression contributing to antimicrobial resistance[15].

Atypical Cell Walls

Several clinically important bacteria have atypical cell wall structures that affect staining and antibiotic susceptibility. Mycobacteria possess a unique cell wall rich in mycolic acids—long-chain fatty acids that create a waxy, hydrophobic barrier[16]. This structure requires acid-fast staining (Ziehl-Neelsen or Kinyoun method) for visualization and confers resistance to many common antibiotics and disinfectants[17]. The extreme example is Mycobacterium tuberculosis, which can survive within macrophages and requires prolonged multi-drug therapy[18].

Bacteria lacking cell walls entirely, such as Mycoplasma species, are unaffected by β-lactam antibiotics and require cell membrane-targeting agents like macrolides or tetracyclines[19]. Mycoplasma pneumoniae, a common cause of atypical pneumonia, cannot be visualized by Gram stain and is identified by serologic testing or PCR[20].

Bacterial Morphology and Arrangements

Bacterial morphology provides important diagnostic clues. Cocci (spherical bacteria) may arrange in pairs (diplococci), chains (streptococci), or clusters (staphylococci)[21]. For example, Streptococcus pneumoniae appears as lancet-shaped diplococci, while Staphylococcus aureus forms grape-like clusters[22].

Bacilli (rod-shaped bacteria) may be short (coccobacilli) or long and filamentous. Certain bacilli, such as Corynebacterium diphtheriae, display characteristic arrangements including palisading (parallel alignment) and V or L shapes. Curved or spiral bacteria include Vibrio (comma-shaped), Campylobacter (S-shaped), spirochetes like Treponema pallidum (tightly coiled), and Borrelia species (loosely coiled)[23].

Bacterial Surface Structures

Capsules are polysaccharide or polypeptide layers external to the cell wall that serve as major virulence factors by inhibiting phagocytosis[24]. Encapsulated bacteria including Streptococcus pneumoniae, Haemophilus influenzae type b, Neisseria meningitidis, and Klebsiella pneumoniae are common causes of meningitis and pneumonia[25]. The Quellung reaction, where capsules swell when exposed to specific antisera, can aid in identification. Polysaccharide vaccines targeting capsular antigens provide protection against these pathogens[26].

Flagella are protein filaments that enable bacterial motility through rotation driven by a proton-motive force[27]. The H antigen refers to flagellar proteins and contributes to bacterial serotyping, particularly in Salmonella species. Peritrichous flagella (surrounding the entire bacterium) are found in E. coli and Salmonella, while polar flagella occur in Vibrio and Pseudomonas.

Pili (fimbriae) are hair-like protein appendages that mediate adherence to host tissues[28]. Common pili facilitate attachment to mucosal surfaces, while sex pili enable conjugation and transfer of genetic material, including antibiotic resistance genes[29]. Type IV pili in Neisseria gonorrhoeae undergo antigenic variation, helping the bacteria evade immune responses[30].

Bacterial Spores

Certain Gram-positive bacteria, notably Bacillus and Clostridium species, form endospores in response to nutrient deprivation[31]. Endospores are metabolically dormant structures with exceptional resistance to heat, radiation, desiccation, and chemical disinfectants[32]. This resistance is conferred by a thick peptidoglycan cortex, small acid-soluble proteins (SASPs) that protect DNA, and dipicolinic acid that stabilizes proteins.

Medically important spore-forming bacteria include Clostridium tetani (tetanus), Clostridium botulinum (botulism), Clostridium perfringens (gas gangrene and food poisoning), Clostridium difficile (pseudomembranous colitis), and Bacillus anthracis (anthrax)[33]. Sterilization of medical equipment requires methods that kill spores, such as autoclaving at 121°C for 15-20 minutes[34].

Bacterial Metabolism and Growth #

Oxygen Requirements

Bacteria are classified based on their oxygen requirements and tolerance[35]. Obligate aerobes require oxygen for growth and use the citric acid cycle and oxidative phosphorylation to generate ATP; examples include Mycobacterium tuberculosis, Nocardia, and Pseudomonas aeruginosa. Obligate anaerobes are killed by oxygen due to lack of catalase and/or superoxide dismutase and inability to neutralize toxic oxygen metabolites; clinically important anaerobes include Clostridium, Bacteroides, and Actinomyces species[36].

Facultative anaerobes can grow with or without oxygen but preferentially use aerobic metabolism when oxygen is available; this category includes most pathogenic bacteria such as Staphylococcus, Streptococcus, and Enterobacteriaceae. Microaerophiles require oxygen but at concentrations lower than atmospheric levels (2-10%); Campylobacter jejuni and Helicobacter pylori are clinically relevant microaerophiles[37].

Aerotolerant anaerobes can tolerate oxygen but do not use it for metabolism; Streptococcus pyogenes is an example. The ability to grow in different oxygen environments correlates with clinical presentations—anaerobic infections typically occur in deep tissue abscesses, aspiration pneumonia, and intra-abdominal infections[38].

Bacterial Growth Curve

Bacterial growth in culture follows a predictable pattern with four phases. The lag phase represents adaptation to the new environment with minimal cell division. The logarithmic (exponential) phase features rapid cell division at a constant rate—bacteria are most susceptible to antibiotics during this phase[39]. The stationary phase occurs when nutrient depletion and waste accumulation cause growth rate to equal death rate. Finally, the death phase shows exponential decline in viable bacteria.

Understanding the growth curve is clinically relevant for antibiotic therapy. β-lactam antibiotics and other cell wall synthesis inhibitors are most effective against rapidly dividing bacteria in the logarithmic phase[40]. Persistent infections may involve bacteria in stationary phase that are less susceptible to standard antibiotics.

Bacterial Genetics

Bacterial genetic material consists of a single circular chromosome containing essential genes and plasmids carrying accessory genes[41]. Plasmids frequently encode antibiotic resistance genes, virulence factors, and metabolic capabilities. The transfer of antibiotic resistance through plasmids has become a major public health concern[42].

Bacteria can acquire new genetic material through three main mechanisms: transformation, transduction, and conjugation[43]. Transformation involves uptake of naked DNA from the environment, as demonstrated in Streptococcus pneumoniae where this phenomenon was first described[44]. Only bacteria that are naturally competent or made competent through laboratory procedures can undergo transformation.

Transduction occurs when bacterial DNA is transferred by bacteriophages (bacterial viruses)[45]. Generalized transduction happens when random bacterial DNA fragments are packaged into phage particles and transferred to recipient bacteria. Specialized transduction involves transfer of specific bacterial genes located near prophage integration sites; examples include transfer of toxin genes such as the diphtheria toxin gene by β-phage to Corynebacterium diphtheriae[46].

Conjugation requires direct cell-to-cell contact through sex pili encoded by fertility (F) plasmids[47]. This mechanism is highly efficient for spreading antibiotic resistance genes among Gram-negative bacteria. During conjugation, the F plasmid or portions of the bacterial chromosome can be transferred from donor to recipient cells.

Transposons and Genetic Recombination

Transposons are mobile genetic elements that can move within or between DNA molecules, facilitating genetic diversity and antibiotic resistance spread[48]. These “jumping genes” can carry resistance genes and insert into chromosomes or plasmids, creating multi-drug resistant bacteria. Some transposons encode their own transposase enzymes that catalyze the movement.

Mutations, both spontaneous and induced, also contribute to bacterial genetic diversity. Point mutations in genes encoding antibiotic targets (such as DNA gyrase for fluoroquinolones or ribosomal RNA for macrolides) are important mechanisms of antibiotic resistance[49]. The high replication rate of bacteria increases the likelihood of spontaneous mutations that may confer survival advantages.

Bacterial Pathogenesis #

Virulence Factors

Bacterial pathogenicity depends on virulence factors that enable colonization, invasion, immune evasion, and host damage[50]. Adhesins mediate attachment to host cells, representing the initial step in infection[51]. Examples include the P pili of uropathogenic E. coli that bind to kidney epithelium and the M protein of Streptococcus pyogenes that facilitates pharyngeal attachment.

Invasins promote bacterial entry into host cells and dissemination through tissues. Shigella species secrete invasins that trigger actin rearrangement and facilitate bacterial internalization into intestinal epithelial cells[52]. Similarly, Yersinia species produce invasins that bind to host cell integrins.

Capsules represent one of the most important virulence factors by inhibiting complement deposition and phagocytosis[53]. The polysaccharide capsule prevents C3b opsonization and masks bacterial surface antigens from immune recognition. Antibodies against capsular antigens can restore phagocytic killing, forming the basis for vaccines against encapsulated bacteria[54].

Bacterial Toxins

Bacterial toxins are classified as exotoxins (secreted proteins) or endotoxins (structural components)[55]. Exotoxins are polypeptides produced by both Gram-positive and Gram-negative bacteria that can cause disease even without live bacteria present. They are generally heat-labile and highly immunogenic, making them targets for vaccine development through toxoid production.

A-B toxins consist of an active (A) subunit and a binding (B) subunit[56]. The B subunit binds to specific cell surface receptors, facilitating entry of the A subunit, which possesses enzymatic activity. Classic examples include diphtheria toxin, which ADP-ribosylates elongation factor-2 (EF-2) to inhibit protein synthesis[57], and cholera toxin, which ADP-ribosylates Gs proteins, leading to constitutive activation of adenylyl cyclase, cAMP accumulation, and massive secretory diarrhea[58].

Shiga toxin, produced by Shigella dysenteriae and enterohemorrhagic E. coli (EHEC), cleaves ribosomal RNA to inhibit protein synthesis[59]. This toxin can cause hemolytic uremic syndrome (HUS) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure[60].

Superantigens bypass normal antigen processing by directly cross-linking MHC class II molecules on antigen-presenting cells with T-cell receptors, leading to massive, non-specific T-cell activation[61]. This triggers excessive cytokine release, potentially causing toxic shock syndrome. Staphylococcus aureus produces toxic shock syndrome toxin-1 (TSST-1), while Streptococcus pyogenes produces streptococcal pyrogenic exotoxins[62].

Endotoxin (lipopolysaccharide) is an integral component of the Gram-negative outer membrane and is released upon bacterial cell death[63]. Unlike exotoxins, endotoxin is heat-stable, weakly immunogenic, and cannot be converted to a toxoid. Endotoxin activates the innate immune system through TLR4, triggering inflammatory cascades that can lead to septic shock[64]. Clinical manifestations include fever, hypotension, disseminated intravascular coagulation, and acute respiratory distress syndrome.

Immune Evasion Mechanisms

Successful pathogens have evolved mechanisms to evade host immune defenses[65]. Antigenic variation involves changing surface proteins to escape antibody recognition, as seen with the pili of Neisseria gonorrhoeae and variant surface glycoproteins of African trypanosomes[66]. The ability to periodically switch expressed antigens allows bacteria to cause chronic or recurrent infections.

Intracellular survival enables bacteria to avoid antibody-mediated immunity and complement[67]. Facultative intracellular pathogens like Mycobacterium tuberculosis, Salmonella typhi, and Listeria monocytogenes can survive and replicate within macrophages by preventing phagosome-lysosome fusion or escaping into the cytoplasm.

Some bacteria produce proteins that degrade immunoglobulins or complement components. Streptococcus pneumoniae produces IgA protease that cleaves secretory IgA, while Staphylococcus aureus protein A binds the Fc region of IgG, preventing opsonization and phagocytosis[68].

Biofilm formation represents an important survival strategy where bacteria embedded in a self-produced extracellular matrix attach to surfaces[69]. Biofilms confer antibiotic resistance through multiple mechanisms including reduced antibiotic penetration, slow growth rate of bacteria in biofilms, and formation of persister cells[70]. Pseudomonas aeruginosa biofilms in cystic fibrosis patients and Staphylococcus epidermidis biofilms on indwelling catheters are clinically significant examples.

Bacterial Classification and Major Pathogens #

Gram-Positive Cocci

Staphylococcus species are catalase-positive, facultative anaerobes that appear in grape-like clusters. Staphylococcus aureus is coagulase-positive and causes a wide spectrum of diseases including skin infections (furuncles, carbuncles, impetigo), pneumonia, osteomyelitis, endocarditis, and toxic shock syndrome[71]. Methicillin-resistant S. aureus (MRSA) has become a major healthcare concern, with resistance mediated by the mecA gene encoding an altered penicillin-binding protein (PBP2a)[72].

Staphylococcus epidermidis and other coagulase-negative staphylococci are normal skin flora but cause infections of prosthetic devices and indwelling catheters through biofilm formation. Staphylococcus saprophyticus is a common cause of urinary tract infections in young, sexually active women.

Streptococcus species are catalase-negative cocci arranged in chains[73]. Classification is based on hemolysis patterns on blood agar and Lancefield grouping based on cell wall carbohydrate antigens. β-hemolytic streptococci cause complete red blood cell lysis, α-hemolytic streptococci cause partial hemolysis with green discoloration, and γ-hemolytic streptococci show no hemolysis.

Streptococcus pyogenes (Group A Streptococcus, GAS) is β-hemolytic and causes pharyngitis, impetigo, erysipelas, cellulitis, necrotizing fasciitis, and scarlet fever[74]. Post-infectious sequelae include acute rheumatic fever and post-streptococcal glomerulonephritis. The M protein is a major virulence factor that prevents phagocytosis through inhibition of complement activation.

Streptococcus agalactiae (Group B Streptococcus, GBS) colonizes the vagina and gastrointestinal tract and is a leading cause of neonatal meningitis and sepsis[75]. Universal prenatal screening and intrapartum antibiotic prophylaxis have reduced early-onset GBS disease.

Streptococcus pneumoniae is an α-hemolytic, lancet-shaped diplococcus with a polysaccharide capsule[76]. It is the most common cause of community-acquired pneumonia, otitis media, sinusitis, and meningitis. The polysaccharide capsule is antiphagocytic, and pneumococcal vaccines target the most common capsular serotypes[77].

Enterococcus species (E. faecalis and E. faecium) are normal gastrointestinal flora that cause urinary tract infections, endocarditis, and intra-abdominal infections. They exhibit intrinsic resistance to many antibiotics and have acquired resistance to vancomycin (VRE), creating significant treatment challenges[78].

Gram-Positive Bacilli

Bacillus anthracis is a spore-forming aerobe that causes anthrax[79]. The anthrax toxin consists of protective antigen, edema factor, and lethal factor, which together cause tissue edema and necrosis. Clinical forms include cutaneous anthrax (painless black eschar), inhalational anthrax (hemorrhagic mediastinitis), and gastrointestinal anthrax.

Clostridium species are obligate anaerobic spore-formers that cause diverse clinical syndromes. Clostridium tetani produces tetanospasmin, a neurotoxin that blocks inhibitory neurotransmitter release (GABA and glycine), causing spastic paralysis and the characteristic risus sardonicus and opisthotonus[80]. Tetanus is prevented by vaccination with tetanus toxoid.

Clostridium botulinum produces botulinum toxin, which blocks acetylcholine release at neuromuscular junctions, causing flaccid paralysis[81]. Infant botulism results from ingestion of spores (associated with honey consumption), while foodborne botulism results from ingestion of preformed toxin in improperly canned foods.

Clostridium perfringens causes gas gangrene (myonecrosis) characterized by rapid tissue destruction, gas production, and systemic toxicity. It also causes food poisoning through enterotoxin production. Clostridium difficile causes antibiotic-associated pseudomembranous colitis through production of toxins A (enterotoxin) and B (cytotoxin)[82]. Treatment includes discontinuation of the offending antibiotic and administration of metronidazole, vancomycin, or fidaxomicin.

Listeria monocytogenes is a facultative intracellular pathogen acquired through contaminated foods, particularly unpasteurized dairy products and deli meats[83]. It can cross the placental barrier and blood-brain barrier, causing meningitis in neonates, elderly, and immunocompromised individuals. Listeria exhibits characteristic tumbling motility and can grow at refrigerator temperatures.

Corynebacterium diphtheriae produces diphtheria toxin (when lysogenized by β-phage carrying the tox gene), which inhibits protein synthesis by ADP-ribosylating EF-2[84]. Clinical diphtheria is characterized by pseudomembrane formation in the pharynx and potential myocarditis and neuropathy from systemic toxin effects. Prevention is through DTaP vaccination.

Gram-Negative Cocci

Neisseria species are oxidase-positive, aerobic diplococci. Neisseria gonorrhoeae causes gonorrhea, characterized by urethritis, cervicitis, and potential disseminated gonococcal infection with septic arthritis and dermatitis[85]. Pelvic inflammatory disease is a serious complication in women leading to infertility and ectopic pregnancy. N. gonorrhoeae exhibits antigenic variation of pili and has developed resistance to multiple antibiotics, necessitating dual therapy with ceftriaxone and azithromycin.

Neisseria meningitidis is a leading cause of bacterial meningitis and meningococcemia[86]. The polysaccharide capsule is antiphagocytic and determines serotypes (A, B, C, W, Y). Meningococcal disease presents with sudden onset of fever, headache, neck stiffness, and petechial or purpuric rash. Waterhouse-Friderichsen syndrome involves bilateral adrenal hemorrhage with acute adrenal insufficiency. Prophylaxis of close contacts with rifampin or ciprofloxacin is essential, and conjugate vaccines are available.

Gram-Negative Bacilli: Enterobacteriaceae

The Enterobacteriaceae family includes numerous important pathogens that are facultative anaerobes, oxidase-negative, and ferment glucose. Escherichia coli is the most common cause of urinary tract infections, with uropathogenic strains possessing P pili for renal epithelium attachment[87]. Enterotoxigenic E. coli (ETEC) produces heat-labile and heat-stable toxins causing traveler’s diarrhea. Enterohemorrhagic E. coli (EHEC), particularly serotype O157:H7, produces Shiga toxin and causes bloody diarrhea and hemolytic uremic syndrome[88]. Enteroinvasive E. coli (EIEC) invades colonic mucosa, mimicking Shigella dysentery.

Salmonella species cause gastroenteritis (non-typhoidal Salmonella) and typhoid fever (Salmonella typhi). Gastroenteritis presents with bloody diarrhea and is commonly acquired from poultry, eggs, and reptiles. Salmonella typhi is transmitted through contaminated food and water, causing sustained bacteremia with fever, abdominal pain, rose spots, and potential intestinal perforation[89]. Chronic carriers harbor bacteria in the gallbladder.

Shigella species cause bacillary dysentery characterized by bloody diarrhea, abdominal cramps, and tenesmus[90]. Shigella invades colonic epithelial cells and produces Shiga toxin. Only a small inoculum (10-100 organisms) is required for infection, and transmission is fecal-oral.

Klebsiella pneumoniae causes pneumonia, particularly in alcoholics and diabetics, characterized by currant jelly sputum due to bloody, mucoid exudate. Klebsiella is also a common cause of urinary tract infections and nosocomial infections. Carbapenem-resistant Klebsiella pneumoniae (CRKP) producing carbapenemases has emerged as a major threat in healthcare settings[91].

Proteus mirabilis is associated with struvite kidney stones due to urease production, which alkalinizes urine and precipitates magnesium ammonium phosphate. Proteus exhibits swarming motility on agar plates.

Yersinia enterocolitica causes enterocolitis with mesenteric adenitis that can mimic appendicitis. Yersinia pestis causes plague, transmitted by fleas from rodent reservoirs, with presentations including bubonic plague (painful lymphadenitis), septicemic plague, and pneumonic plague[92].

Serratia marcescens produces a red pigment and causes nosocomial infections, particularly in catheterized patients and those with indwelling devices.

Gram-Negative Bacilli: Non-Enterobacteriaceae

Pseudomonas aeruginosa is an obligate aerobe with oxidase-positive reaction and characteristic fruity grape-like odor. It produces pyocyanin (blue-green pigment) and pyoverdin. P. aeruginosa causes nosocomial pneumonia (particularly in ventilated patients), urinary tract infections, burn wound infections, and external otitis (“swimmer’s ear”)[93]. In cystic fibrosis patients, chronic Pseudomonas infection with biofilm formation leads to progressive lung damage. The organism exhibits intrinsic resistance to many antibiotics through efflux pumps and low outer membrane permeability.

Haemophilus influenzae is a small, pleomorphic coccobacillus requiring factors V (NAD+) and X (hemin) for growth. Before routine vaccination, H. influenzae type b (Hib) was the leading cause of bacterial meningitis in children[94]. The polysaccharide capsule (polyribosylribitol phosphate, PRP) is the basis for the conjugate vaccine. Non-typeable H. influenzae causes otitis media, sinusitis, and exacerbations of chronic obstructive pulmonary disease.

Bordetella pertussis causes whooping cough (pertussis), characterized by paroxysmal coughing with inspiratory whoop and post-tussive emesis[95]. Pertussis toxin ADP-ribosylates Gi proteins, disrupting signal transduction and causing lymphocytosis. Prevention is through vaccination with acellular pertussis vaccine in combination with diphtheria and tetanus toxoids (DTaP).

Legionella pneumophila is an intracellular pathogen that grows in water systems and is transmitted through aerosols from cooling towers, hot water tanks, and air conditioning systems. It causes Legionnaires’ disease (atypical pneumonia) and Pontiac fever (self-limited flu-like illness)[96]. Legionella requires special culture media (buffered charcoal yeast extract agar) and is diagnosed by urinary antigen test.

Vibrio cholerae causes cholera, characterized by massive watery “rice-water” diarrhea leading to severe dehydration and electrolyte imbalance[97]. Cholera toxin permanently activates adenylyl cyclase through ADP-ribosylation of Gs proteins, causing cAMP-mediated chloride and water secretion. Treatment focuses on oral or intravenous rehydration.

Campylobacter jejuni is a curved, motile, microaerophilic bacterium transmitted through contaminated poultry, unpasteurized milk, and water. It causes bloody diarrhea and is associated with subsequent development of Guillain-Barré syndrome due to molecular mimicry between bacterial antigens and nerve gangliosides[98].

Helicobacter pylori is a spiral, microaerophilic bacterium that colonizes gastric mucosa[99]. It produces urease, which neutralizes gastric acid and enables survival in the acidic environment. H. pylori causes chronic gastritis, peptic ulcer disease, and is associated with gastric adenocarcinoma and MALT lymphoma. Diagnosis includes urea breath test, stool antigen test, and biopsy with rapid urease test. Treatment involves triple or quadruple therapy combining proton pump inhibitors with antibiotics.

Bacteroides fragilis is the most common obligate anaerobe in the gastrointestinal tract and is a leading cause of intra-abdominal abscesses, particularly after bowel perforation or surgery[100]. It possesses a polysaccharide capsule that promotes abscess formation and inhibits phagocytosis. Bacteroides produces β-lactamases, requiring treatment with metronidazole, carbapenems, or β-lactam/β-lactamase inhibitor combinations.

Spirochetes

Spirochetes are thin, spiral bacteria with unique motility conferred by axial filaments (endoflagella) located in the periplasmic space. Treponema pallidum causes syphilis, a sexually transmitted disease with distinct stages[101]. Primary syphilis presents with a painless chancre at the inoculation site. Secondary syphilis features diffuse maculopapular rash including palms and soles, condyloma lata, and lymphadenopathy. Tertiary syphilis can manifest as gummas (granulomatous lesions), aortitis, and neurosyphilis. T. pallidum cannot be cultured in vitro; diagnosis relies on darkfield microscopy and serologic tests including non-treponemal (VDRL, RPR) and treponemal (FTA-ABS, TP-PA) antibody tests.

Borrelia burgdorferi causes Lyme disease, transmitted by Ixodes tick bites[102]. Early localized disease features erythema migrans, a characteristic expanding rash with central clearing. Early disseminated disease can involve cardiac (AV block) and neurologic (facial nerve palsy, meningitis) manifestations. Late disease presents with chronic arthritis and chronic encephalopathy. Diagnosis is primarily clinical, supported by two-tier serologic testing.

Leptospira interrogans causes leptospirosis, acquired through contact with water contaminated by infected animal urine. Clinical presentation ranges from mild flu-like illness to Weil disease, characterized by jaundice, renal failure, and hemorrhage.

Mycobacteria

Mycobacteria are acid-fast bacilli with a mycolic acid-rich cell wall that resists decolorization by acid-alcohol after carbolfuchsin staining[103]. Mycobacterium tuberculosis is an obligate aerobe transmitted via respiratory droplets. Primary tuberculosis typically affects the middle or lower lung lobes with hilar lymphadenopathy (Ghon complex). Most infections are contained by cell-mediated immunity, with bacteria persisting in a dormant state (latent TB). Reactivation tuberculosis preferentially affects the upper lobes due to higher oxygen tension and presents with fever, night sweats, weight loss, cough, and hemoptysis[104]. Diagnosis requires sputum acid-fast bacilli smear and culture, with molecular tests (nucleic acid amplification) providing rapid results. Treatment requires prolonged multi-drug therapy with rifampin, isoniazid, pyrazinamide, and ethambutol to prevent resistance.

Mycobacterium leprae causes leprosy (Hansen disease), characterized by skin lesions and peripheral neuropathy. Tuberculoid leprosy involves a strong cell-mediated immune response with few organisms and well-formed granulomas. Lepromatous leprosy reflects impaired cell-mediated immunity with numerous organisms and diffuse tissue infiltration. Diagnosis is by skin biopsy showing acid-fast bacilli.

Nontuberculous mycobacteria (NTM) include Mycobacterium avium complex (MAC), which causes disseminated infection in AIDS patients with CD4 counts below 50 cells/μL, and pulmonary disease in patients with structural lung disease. Mycobacterium marinum causes skin infections after aquatic exposure.

Atypical Bacteria

Mycoplasma pneumoniae lacks a cell wall, making it resistant to β-lactam antibiotics[105]. It causes atypical pneumonia characterized by gradual onset, nonproductive cough, and extrapulmonary manifestations including bullous myringitis and cold agglutinins (IgM antibodies against RBCs). Diagnosis is by serology or PCR, and treatment involves macrolides, tetracyclines, or fluoroquinolones.

Chlamydia species are obligate intracellular bacteria that cannot synthesize ATP and must obtain it from host cells[106]. Chlamydia trachomatis causes sexually transmitted infections including urethritis, cervicitis, and pelvic inflammatory disease. Serotypes A-C cause trachoma, a leading infectious cause of blindness. Serotypes L1-L3 cause lymphogranuloma venereum. Chlamydia pneumoniae causes atypical pneumonia. Chlamydophila psittaci is transmitted from birds and causes psittacosis.

Rickettsia species are obligate intracellular Gram-negative bacteria transmitted by arthropod vectors. Rickettsia rickettsii causes Rocky Mountain spotted fever, characterized by fever, headache, and centripetal rash (starting on wrists and ankles, spreading centrally)[107]. The organisms invade vascular endothelium, causing vasculitis. Diagnosis is clinical, and treatment with doxycycline should be initiated promptly.

Antimicrobial Resistance #

Antimicrobial resistance has emerged as one of the most pressing public health threats globally[108]. Bacteria develop resistance through multiple mechanisms including enzymatic drug inactivation, target site modification, decreased drug uptake, and increased drug efflux[109].

β-lactamase production is the most common resistance mechanism against β-lactam antibiotics[110]. Extended-spectrum β-lactamases (ESBLs) confer resistance to third-generation cephalosporins and are prevalent in Enterobacteriaceae. Carbapenemases, including Klebsiella pneumoniae carbapenemases (KPC) and New Delhi metallo-β-lactamases (NDM), hydrolyze carbapenems and represent a critical threat[111].

Methicillin resistance in Staphylococcus aureus results from acquisition of the mecA gene encoding penicillin-binding protein 2a (PBP2a), which has low affinity for β-lactam antibiotics[112]. MRSA infections require treatment with vancomycin, daptomycin, or linezolid.

Vancomycin resistance in enterococci (VRE) involves alteration of the peptidoglycan terminal amino acids from D-Ala-D-Ala to D-Ala-D-Lac, reducing vancomycin binding[113]. VRE has also emerged in rare Staphylococcus aureus strains (VRSA).

Target site modification through mutations in chromosomal genes is important for fluoroquinolone resistance (DNA gyrase and topoisomerase IV mutations) and macrolide resistance (ribosomal RNA mutations)[114]. Ribosomal protection proteins and enzymatic modification also contribute to macrolide resistance.

Efflux pumps actively transport antibiotics out of bacterial cells and can confer multidrug resistance[115]. These pumps are particularly important in Pseudomonas aeruginosa resistance.

Plasmid-mediated resistance gene transfer through conjugation enables rapid spread of resistance among bacterial populations. The global dissemination of resistance genes emphasizes the importance of antimicrobial stewardship and infection control measures.

Laboratory Diagnosis #

Proper specimen collection, transport, and processing are critical for accurate microbiologic diagnosis. Gram staining provides rapid preliminary identification based on morphology and staining characteristics. Culture on appropriate media (blood agar, MacConkey agar, chocolate agar, specialized media) allows isolation and identification.

Biochemical tests differentiate bacteria based on metabolic capabilities. Key tests include catalase (positive in staphylococci, negative in streptococci), coagulase (positive in S. aureus), oxidase (positive in Neisseria and Pseudomonas), and various sugar fermentation tests.

Serologic testing detects antibodies or antigens in patient samples and is useful for organisms difficult to culture (Treponema pallidum, Coxiella burnetii, Chlamydia). Molecular methods including polymerase chain reaction (PCR) provide rapid, sensitive, and specific detection of bacterial pathogens. Mass spectrometry (MALDI-TOF) has revolutionized bacterial identification by analyzing protein profiles[116].

Antimicrobial susceptibility testing determines the minimum inhibitory concentration (MIC) of antibiotics and guides therapy. Methods include disk diffusion (Kirby-Bauer), broth dilution, and automated systems.

Conclusion #

Bacteriology encompasses diverse organisms with varied structural, metabolic, and pathogenic characteristics. Understanding bacterial classification, virulence mechanisms, host-pathogen interactions, and antimicrobial resistance is essential for medical practice.

References #

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