Bacteria & Bacterial Diseases
Bacterial morphology & Structure
Bacterium (single copy)/ Bacteria (many copies)
Bacterium: It is a gel-like matrix made up of water, enzymes, nutrients, wastes, gases and
contains cell structures such as ribosomes, a chromosome, and mobile genetic elements
(these may include plasmids, pathogenicity islands and transposons). The cell envelope
encases the cytoplasm and all its components.
Bacteria do not have a membrane enclosed nucleus; therefore known as prokaryotes
(Greek word for membrane-less nucleus microbes).
N/B
Eukaryotes are cells with membrane enclosed nucleus e.g. plants and animals cells.
Bacteria: they form the major component of the earth’s biosphere and are significant parts
of animal and plant microbiota.
Bacterial morphology: i.e shape of various bacteria as observed microscopically (Figure
1).
These are the common forms:
a. Circular (coccus)
b. Rod-like (bacillus)
c. Elongated rod-like (Filamentous)
d. Coccobacilli (intermediate shape between sphere and rod-like)
e. Cork-screw like appearance (spirochaete)
f. Comma or S-shaped/curved
The bacteria may have a cell-wall enclosing a plasma (cytoplasmic) membrane or just
plasma membrane.
The structure and biochemical composition of the cell-wall varies from one bacterial
genus (or even specie) to another.
Cell-wall; could be composed of only
- Peptidoglycan compound
thick peptidoglycan (murein) layer (mainly with Gram +ve bacteria,
where it is > 10 layers),
murein is a unique future of just the bacteria and specifically Gram +ve
bacteria; murein consist of N-acetylglucosamine (NAG) and N-
acetylmuramic acid (NAM) glucose derivatives alternated in long
chains. These chains (NAG & NAM) are linked by four four amino
acids to form a tetrapeptide. These amino acids are 1). L-alanine, 2).
D-glutamine, 3). L-lysine (meso-diaminopimelic acid [DPA]) and 4).
D-alanine.
In Gram +ve bacteria the above cell-wall structure is further reinforced
with teichoic acid (a glycopolymer compound) that are embedded
within the murein layers.
Teichoic acids assists the bacterium to withstand high temperatures,
high salt concentrations, β-lactam antibiotics (it makes the bacteria
resistant to these drugs after undergoing some mutation).
Is often the target of a number of antibiotics such as beta (β)-lactam
drugs like, penicillin, cephalosporin, carbapenem, and monobactam
subfamilies.
The primary resistance mechanisms used by Gram-positive bacteria against
the above class of antibiotics are different from those used by the Gram-
negative bacteria.
Gram +ve bacteria resistance mechanisms to β-lactam antibiotics
involves structural changes to the specific enzyme targets (the targets
are penicillin-binding proteins [PBPs]) of the β-lactam antibiotics
render these enzymes less reactive to the β-lactam is identical to the
mechanism used by the bacterial producers of the β-lactams.
The PBPs are the primary catalysts for the synthesis and remodeling
of the peptidoglycan cell wall of bacteria.
Some also, produce β-lactamase enzymes to inactivate beta-lactam
antibiotics.
N/B
When teichoic acid is attached to peptidoglycan it is called wall
teichoic acid (WTA), but if linked to cell membrane via lipid anchor then
it is lipoteichoic acid (LTA).
Teichoic Acids: Teichoic acids are polyol phosphate polymers bearing
a strong negative charge. They are covalently linked to the
peptidoglycan in some Gram-positive bacteria. They are strongly
antigenic, but are generally absent in Gram-negative bacteria.
Lipoteichoic Acids: Lipoteichoic acids as membrane teichoic acids are
polymers of amphiphitic glycophosphates with the lipophilic glycolipid
and anchored in the cytoplasmic membrane. They are antigenic,
cytotoxic and adhesins (e.g., Streptococcus pyogenes).
thin layer of peptidoglycan enclosed by a thick lipid layer
lipopolysaccharide (LPS); this is a future of Gram –ve bacteria; it is
exist as one or two layers but covered by lipid (LPS) on the outer part.
LPS is made up of three different components:
1. The O-antigen or O-polysaccharide, which represents the
outermost part of the structure.
2. The core polysaccharide.
3. Lipid A, which anchors the LPS into the outer membrane.
N/B.. LPS is associated with Gram –ve bacterial virulence;
O-antigen is known to illicit severe immune reactions that might
result to death in humans/animals as the case with E. coli O157
infection
Lipid A; acts as a toxin, specifically an endotoxin, causing general
symptoms of illness such as fever and diarrhea. While a large
content of it in the bloodstream can trigger endotoxic shock, a
body-wide inflammatory response that can be life-threatening.
Is (peptidoglycan) often the target of a number of antibiotics such as beta
(β)-lactam drugs like, penicillin, cephalosporin, carbapenem, and
monobactam subfamilies when treating diseases associated with Gram –ve
bacteria.
Gram-negative bacteria resistance mechanisms to β-lactam antibiotics
is via expression of enzyme(s) that hydrolytically destroy the β-lactam
like, β-lactamase, metallo-β-lactamases, etc.
The mycobacterial cell wall resembles both the Gram-positive and
Gram-negative cell envelope by having a Peptidoglycan (PG) layer
nearly as thick as the former and an outer, waxy layer mimicking the
outer membrane of the latter.
PG layer, mycolic acid (MA) [waxy layer] and arabinogalactan (AG) are
the main component of mycobacterium (Mycobacterium sp) cell wall.
However, bacteria of the phylum Tenericutes don’t possess
peptidoglycan compounds which makes them innately resistant
peptidoglycan targeting antibiotics such as penicillin.
These bacteria are mainly pathogenic strains in the Mycoplasmatales
order (which encompasses the genera such as Mycoplasma spp,
Ureaplasma, Entomoplasma and Spiroplasma). E.g.
M. pneumonia (associated respiratory infections)
M. hominis (associated pelvic inflammatory infections)
M. genitalium (infections of the genitals)
Ureaplasma urealyticum and Ureaplasma parvum (all cause
infection of the reproductive tracks like urethra, vagina, pneumonia
[newborn babies]).
Figure 1: Various morphology of bacteria.
Capsule: formed primarily from long-chain polysaccharides with repeat-unit structures or
polypeptide and, it is 98% water and 2% polysaccharide or glycoprotein/ polypeptide or
both.
- A given bacterial species can produce a range of capsular polysaccharides (CPSs)
with different structures and these help distinguish isolates by serotyping, as is the
case with Escherichia coli K antigens.
- Capsules are important virulence factors for many pathogens (e,g B. anthracis); help
to prevent bacterial desiccation, foil phagocytosis by host cells or reduce
complement-mediated lysis, for attachment (e.g Streptococcus mutants that causes
dental carriers).
- In addition, CPSs are widely used in vaccines deployed in clinical practice
worldwide.
Flagella (flagellum): are complex and well-honed organelles that provide swimming and
swarming motilities and further play a central role in adhesion, biofilm formation, and host
invasion.
A typical bacterial flagellum consists of six components: a basal body (including MS ring, P
ring, and L ring), a motor, a switch, a hook, a filament, and an export apparatus.
Are common among Gram –ve bacteria such as E.coli, Salmonella spp,
A figure of flagella structure of bacteria A-Monotrichous; B-Lophotrichous; C-
Amphitrichous; D-Peritrichous
Pilli (fimbriea): are hair-like long proteinaceous appendages on bacterial cell surface used
for interaction with the external environments.
- Are primarily composed of oligomeric pilin proteins, which arrange helically to
form a cylinder. New pilin protein molecules insert into the base of the pilus. Pili
are antigenic, and genes encoding pili can be located in the bacterial
chromosome or in plasmids. Pili are not locomotive structures.
- Are classified into ordinary pilus or sex pilus according to their morphology,
distribution, and function.
- Distinct pilus classes can be identified on basis of their assembly pathways,
including chaperone-usher pili, type V pili, type IV pili, curli and fap fibers,
conjugative and type IV secretion pili, as well as sortase-mediated pili.
- Pili play versatile roles in bacterial physiology, and can be involved in adhesion
and host cell invasion, DNA and protein secretion and uptake, biofilm formation.
Bacterial classification (PLEASE READ ON YOUR OWN)
1. Microscopic morphology
2. Macroscopic morphology – colony appearance
3. Physiological / biochemical characteristics
4. Chemical analysis
5. Serological analysis
6. Genetic and molecular analysis
• G + C base composition
• DNA analysis using genetic probes
• Nucleic acid sequencing and rRNA analysis
Antibiotics
- Are medicinal molecules/substances that inhibit bacterial growth or kill
bacteria.
- Are classified as bacteriostatic (inhibit bacterial growth and reproduction)
[Create a list of these antibiotics] or bactericidal (destroys the bacteria)
[Create a list of these antibiotics] assignment
Types of antibiotics
1. Beta-lactam antibiotics ( possess 3-carbon and 1-nitrogen ring) and they includes
penicillins and its derivatives like amoxicillin,
Cephalosporins. They contain a 7-aminocephalosporanic acid nucleus and
side-chain containing 3,6-dihydro-2 H-1,3- thiazane rings. Cephalosporins are
traditionally divided into five classes or generations, although acceptance for
this terminology is not universal.
Carbapenems. Their defining structure is a carbapenem coupled to a beta-
lactam ring that confers protection against most beta-lactamases, although
resistance to these compounds is a significant issue and occurs mainly
among gram-negative pathogens (e.g., Klebsiella
pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) which
produce different classes of beta-lactamases termed as carbapenemase.
Monobactams. The beta-lactam ring stands alone and not fused to another
ring.
Beta-lactamase inhibitors. They work primarily by inactivating serine beta-
lactamases, which are enzymes that hydrolyze and inactivate the beta-lactam
ring (especially in gram-negative bacteria). These agents include the first-
generation beta-lactamase inhibitors (clavulanic acid, sulbactam, and
tazobactam) and the newer avibactam and vaborbactam that are active
against carbapenemase such as Klebsiella pneumoniae carbapenemase
(KPC).
2. Aminoglycosides: are broad-spectrum, bactericidal antibiotics (such as gentamicin,
amikacin, tobramycin, neomycin, and streptomycin).
3. Glycopeptide it includes vancomycin and lipoglycopeptide like teicoplanin and
synthetic derivatives such as telavancin, dalbavancin, and oritavancin.
4. Macrolides: attaches to 50S ribosomal subunit to inhibit proteinsynthesis. They
include erythromycin, azithromycin, clarithromycin, and roxithromycin (are
bacteriostatic drugs)
5. Rifampicin: inhibit bacterial RNA elongation; it includes drugs like rifampin,
rifapentine, and rifabutin.
6. tetracyclines (such as tetracycline and doxycycline)– can be used to treat a wide
range of infections, but are commonly used to treat moderate to severe acne
and rosacea
7. fluoroquinolones (such as ciprofloxacin and levofloxacin) – broad-spectrum
antibiotics that can be used to treat a wide range of infections
Antibiotic sensitivity cultures
There are a number of ways for determining bacterial antibiotic sensitivity. However, for
each method usually there is need for a pure bacterial isolate. The rapid advancement of
diagnostic technique has in certain instance eliminated the need for culture and especially
when dealing with either slow growing bacteria (e.g Mycobacteria spp) or highly contagious
lethal bacteria like Bacillus anthracis.
Some of the methods currently used are
- Kirby-bauer (disk diffusion) method.
- Broth dilution test
- Antimicrobial gradient method
- Molecular method such as PCR, NGS (next generation sequencing), Nanopore
sequencing, matrix-assisted laser desorption/ionization time-of-flight
(MALDI-TOF) mass spectrometry.
Factors enhancing pathogenicity of bacteria