Microbiology IV ; DOMAIN BACTERIA

DOMAIN BACTERIA
A. Taxonomy and nomenclature
1. classification. Bacteria (or Eubacteria) are grouped and named primarily based on morphologic and biochemical characteristics (e.g., the nature of the cell wall, staining characteristics, ability to use oxygen, ability to form endospores). DNA technology has led to the reclassification of some organisms based on DNA sequences and homology. Bacteria are named using the binomial Linnaean system as a genus and species; some species are classified with subspecies or strain designations.

2. Morphology is the classification of bacteria by shape and structure.
a. Colony morphology is based on the size, color, shape, and texture of colonies that are grown in pure culture on an agar plate. Each colony originates from a colony-forming unit (CFU), consisting of a single cell or group of adherent cells.

b. Microscopic morphology describes bacteria based on the size, shape, and arrangement of the cells.

3. Stains. Because of their small size and relative transparency, bacteria must be stained to be visible under the light microscope. Staining characteristics may be used in classification. The major types of staining reactions are the following:
a. The simple stain uses a single dye (e.g., methylene blue, basic fuchsin, and crystal violet) to color the cells.
b. The gram stain is a differential staining procedure in which the purple stain is retained in the thick peptidoglycan layer of the gram-positive bacteria, whereas the color is removed by an
alcohol rinse from the thinner gram-negative walls. The gram-negative cells are then stained red by the counterstain.
c. The acid-fast stain uses a procedure to stain cells that have an outer layer of a waxy lipid (acid-fast, stained red). This waxy layer prevents removal of the stain by an acid rinse. The stain is removed from cells that lack the waxy layer, which are then counterstained blue (non–acid-fast). Bacteria of the genus Mycobacterium are acid-fast bacilli (AFB).
d. The endospore stain involves a procedure that uses heat to help dye enter the endospore
e. The capsule stain is a colloidal suspension that is excluded from areas occupied by capsule and allows detection of the unstained capsular material.

4. Bacterial cell shape and arrangement
a. Cocci are spherical and exist in chains (e.g., Streptococcus species), pairs/diplococci (e.g.,
Neisseria gonorrhoeae), and clusters (e.g., Staphylococcus species).
b. Bacilli are cylindrical and rod-shaped organisms (e.g., pseudomonads, Escherichia).
c. Coccobacilli are short, rounded rods (e.g., Haemophilus).
d. Spirochetes and spirilla are helical like a corkscrew (e.g., Treponema pallidum).
e. Vibrios are comma-shaped rods (e.g., Vibrio cholerae).
f. Pleomorphic organisms exist in varied forms (e.g., Legionella, Corynebacterium).

B. Structure of the prokaryotic cell
1. Overview. Prokaryotic cells (bacteria) are small and structurally different than eukaryotic organisms in a number of ways. Bacteria
a. have a complex cell wall structure,
b. lack internal membrane-bound organelles (e.g., nucleus, plastids, endoplasmic reticulum, vacuoles),
c. multiply asexually by binary fission rather than by mitosis or meiosis,
d. use 70S ribosomes rather than 80S ribosomes for protein synthesis, and
e. possess a single supercoiled circular chromosome.

2. Cytoplasmic structures
a. Bacterial ribosomes are the sites of protein synthesis—the process whereby the messenger RNA (mRNA) code is translated into an amino acid sequence . In addition to being smaller (70S rather than 80S), bacterial ribosomes are significantly different from those of eukaryotic cells and are targets for antibacterial therapies. Bacterial ribosomes are not associated with membranes.
b. The bacterial chromosome is typically a single, double-stranded, circular molecule that is
contained within a discrete area of the cell known as the nucleoid.
c. Plasmids are small, circular, extrachromosomal DNAs that are present in some bacteria. They often contain virulence genes, antibiotic resistance, or other genetic elements, such as transposons (is a DNA sequence that can change its position within the genome).

3. The cytoplasmic membrane of bacteria is a phospholipid bilayer similar to eukaryotic membranes, except eukaryotic membranes contain sterols (e.g., cholesterol), whereas bacteria, with the exception of mycoplasmas, do not. The phospholipid arrangement creates a permeability barrier by establishing hydrophilic regions (glycerol phosphates) that flank a hydrophobic core (fatty acids). The cytoplasmic membrane and the proteins embedded within are responsible for several important functions of the bacterium.
a. Transport of nutrients occurs by several mechanisms.
(1) Facilitated diffusion is the passive diffusion of a substrate across the membrane using specific carrier proteins.
(2) Active transport is the movement of molecules against a concentration gradient (from lower concentration outside of the cell to higher concentration inside the cell), which requires energy.
(3) Group translocation is a variation of active transport in which the bacterial cell modifies the transported molecule such that the molecule can no longer leave the cell (e.g., phosphorylated glucose).
b. Energy production and the electron transport chain occur across the cytoplasmic membrane.
c. Cell wall biosynthesis occurs at the outer surface of the cytoplasmic membrane with the transport of cell wall precursors across the membrane for further assembly outside of the cytoplasm. Actinlike filaments may also line the cytoplasmic membrane for shape and septum
formation during cell division.
d. Secretion systems that traverse the cytoplasmic membrane may be employed to translocate proteins across the cytoplasmic membrane to the outside of the bacterium (gram-positive bacteria) or to the periplasmic space (gram-negative organisms).

4. All bacteria have a cell wall composed of peptidoglycan, except mycoplasmas.
The cell wall is a rigid structure that provides the general shape of the cell and functions to protect the cell from osmotic shock. The peptidoglycan of the cell wall is composed of repeating disaccharide units (a polymer of N-acetylglucosamine and N-acetylmuramic acid), with amino acid side chains that are covalently linked to amino acid side chains from disaccharide units elsewhere in the polymer, forming a stable cross-linked structure. The designations gram positive, gram negative, and acid fast are based on fundamental differences in the components of the cell wall and associated structures. Owing to the uniqueness and the importance of the cell wall to bacterial viability, it is the target of many antimicrobial agents (will be discussed later ).

a. Gram-positive organisms have a thick cell wall (approximately 40 layers thick), which is 90% peptidoglycan, with extensive cross-linking. Teichoic acid and lipoteichoic acid are polymers of glycerol or ribitol phosphodiesters that contribute to the structure of the gram-positive cell wall; lipoteichoic acid contains a fatty acid that anchors the cell wall to the cytoplasmic membrane. Additional cell wall–associated proteins and polysaccharides may serve as antigenic determinants.

b. Acid-fast bacteria (mycobacteria) have a thick peptidoglycan cell wall, which is surrounded by a waxlike coat of mycolic acid and glycolipids that is impermeable to many substances and imparts resistance to many disinfectants and antibiotics.

c. Gram-negative cell walls are more complex structurally and chemically, although they are thinner and do not contain teichoic or lipoteichoic acid.

(1) Unique to gram-negative bacteria is an outer membrane, external to the cell wall, that acts as a permeability barrier to large molecules (e.g., lysozyme) and hydrophobic molecules (e.g., some antimicrobials). The outer membrane is an asymmetric bilayer, which consists of an inner leaflet with phospholipids much like those of the cytoplasmic membrane and an outer leaflet composed primarily of lipopolysaccharide (LPS). LPS, which is also known as endotoxin, is toxic to humans and is a potent activator of the immune response. LPS is responsible for many of the features of infections by gram-negative bacteria, including inflammation, fever, and shock. LPS is composed of three parts:
(a) Lipid A consists of a disaccharide backbone with attached fatty acids. It is an integral component of the outer membrane and is responsible for the endotoxin activity.
(b) Core polysaccharide is a branched polysaccharide of 9–12 sugars. Most bacteria within a genus will share conserved core polysaccharide structures.
(c) The O-antigen portion, which consists of 50–100 repeating saccharide units, is attached to the core polysaccharide and extends away from the bacterial surface. The O-antigen composition and structure can vary within a bacterial species and is often used to distinguish specific serotypes (e.g., O157, strains of enterohemorrhagic Escherichia coli).

(2) Specialized secretion systems used by gram-negative organisms translocate proteins from the cytoplasm across both membranes to the outside. The type III secretion system, which is a virulence factor used by many gram-negative pathogens, translocates proteins from the bacterial cytoplasm across both bacterial membranes and across nearby host cell membranes into the host cell cytoplasm to effect changes in the eukaryotic cell.

(3) Proteins associated with the outer membrane include receptors, structural proteins, and components of transport and secretory systems. Porins are transmembrane proteins that form pores to allow diffusion of small hydrophilic molecules through the outer membrane.

(4) The periplasmic space, an area between the cytoplasmic and outer membranes of gram-negative bacteria, contains components of transport systems (e.g., iron, sugars, metabolites) and hydrolytic enzymes (e.g., proteases, phospholipases, nucleases, and carbohydrate-degrading enzymes) for the breakdown of macromolecules. Enzymes for the breakdown of antimicrobials may also be located in the periplasmic space (e.g.,b-lactamase).

5. External structures
a. Capsule is an adherent, usually polysaccharide surface coat (glycocalyx); however, the capsule of Bacillus anthracis is polypeptide. Not all bacteria are able to make a capsule, and those that do often do not continue to make the capsule upon culture in the lab. Antigenic differences among capsules can be used to identify strains within a single species of bacteria (e.g., Streptococcus pneumoniae, Haemophilus influenzae type b). The capsule is a major virulence factor owing to the following features:
(1) Acts as a barrier to toxic hydrophobic molecules
(2) Prevents phagocytosis of the organism by macrophages and neutrophils
(3) Aids in adherence of the organism to host cells and nonbiological surfaces
b. Flagella are threadlike appendages of helically coiled protein subunits (flagellin) that are used by some bacteria for movement. Flagella are anchored in the bacterial membrane and their rotation is driven by proton motive force. A bacterium may have one or more flagella anchored at different parts of the cell. The direction of the flagella rotation and thus the type of movement is influenced by chemoreceptors and signaling pathways that facilitate movement toward chemoattractants (chemotaxis) and away from repellants. Flagella express antigenic and strain determinants (typically the H antigen in strain designations). Periplasmic flagella, also called axial filaments, used by spirochetes, are positioned beneath the bacterial outer membrane. Movement of the axial filament leads to a corkscrew type of motion that facilitates movement through viscous environments.
c. Pili (fimbriae) are proteinaceous, hairlike structures on the outside of bacteria that promote adherence to surfaces, host cells, or other bacteria and are therefore an important virulence factor for some bacteria. F pili (sex pili), which are encoded by a plasmid (F), bind to other bacteria for the transfer of large segments of DNA between bacterial cells.

6. Endospores or bacterial spores are dehydrated multishelled structures formed by some grampositive organisms (Clostridium and Bacillus) in response to adverse conditions. The endospore contains the bacterial DNA surrounded by a thick, keratin-like coat that imparts resistance to heat, dehydration, radiation, and chemicals. It is not metabolically active and can remain dormant for years. Upon exposure to water and nutrients, the endospore may once again become metabolically active, germinating into the vegetative state.

C. Microbial physiology
1. Nutritional requirements. Bacteria use a wide variety of nutrients to obtain energy and to construct new cellular components. The minimum requirement for growth is a source of carbon and nitrogen, an energy source, water, and various ions. Beyond these essentials, different bacteria have different requirements for exogenous sources of the elements for the construction of cellular components (DNA, carbohydrates, and proteins) and processes (enzymes). Most bacteria of medical importance would be considered heterotrophs (cannot fix carbon and uses organic carbon for growth. This contrasts with autotrophs, such as plants and algae, which can use energy from sunlight (photoautotrophs) or inorganic compounds (lithoautotrophs) to produce organic compounds) in that they require an exogenous source for one or more essential metabolites. Growth requirements and metabolic by-products can be a means of identifying bacteria.

2. Oxygen requirements
a. Aerobes have the ability to grow in the presence of atmospheric oxygen.
(1) Obligate aerobes depend completely on oxygen for growth. Oxygen serves as the terminal electron acceptor in aerobic respiration.
(2) Aerotolerant bacteria have the ability to grow with or without molecular oxygen, although they do not use oxygen for respiration.
b. Anaerobes have the ability to grow without oxygen.
(1) Obligate anaerobes do not tolerate the presence of oxygen and must grow in an environment free of oxygen. Many of these bacterial strains lack catalase and superoxide dismutase, enzymes that protect cells from the destructive oxidizing by-products normally produced under aerobic conditions (e.g., hydrogen peroxide, superoxide anions).
(2) Facultative anaerobes do not require oxygen but grow better in its presence.
c. Microaerophiles require oxygen levels below normal atmospheric pressures for growth (e.g., Helicobacter pylori).

3. Bacterial growth occurs by binary fission and can be measured as a doubling time or generation time. Growth can be plotted as the log of the cell number versus time to produce a curve with four distinct phases.
a. The lag phase is a transition period during which the bacteria are replicating the chromosomal DNA and producing the enzymes needed for the new environment.
b. During logarithmic (log) phase, division occurs at a constant and maximal rate, and the number of cells increases in a geometric progression. Under ideal growth conditions, the generation time varies among species over a range of minutes (15 to 20 mins for Escherichia) to hours (15 to 20 hrs for Mycobacterium tuberculosis). Because the cell wall is being synthesized rapidly, bacterial cells are most susceptible to cell wall inhibitors during this phase.
c. In stationary phase, the growth rate tapers off such that growth and death rates are nearly equal, and a fairly constant population of viable cells results.
d. Death phase occurs as the number of viable cells declines and the environment accumulates toxic wastes and autolytic enzymes.

D. Metabolism and energy production
1. Microorganisms derive energy through the controlled breakdown of various organic substrates (carbohydrates, lipids, proteins) to produce usable energy, typically as adenosine triphosphate (ATP).
a. Substrate-level phosphorylation is the process by which energy is directly transferred from an intermediate metabolic compound to generate ATP from adenosine diphosphate (ADP).
b. Oxidative phosphorylation generates ATP through a series of oxidation reactions in which electrons from nicotinamide-adenine dinucleotide (NAD or its reduced form, NADH) or flavin adenine dinucleotide (FAD or its reduced form, FADH2) are transferred through electron carriers, and ultimately to a final inorganic acceptor.
This process creates a proton gradient that is used to fuel the generation of ATP. In the absence of oxygen, substrate level phosphorylation is typically the primary means of energy production; however, substrate level phosphorylation coupled with oxidative phosphorylation is a more efficient means of generating energy but requires a final inorganic electron acceptor (usually oxygen).

2. The glycolytic (glycolysis) or Embden-Meyerhof-Parnas (EMP) pathway, the first step in fermentation and respiration, converts glucose into pyruvate, with the net yield of two molecules of ATP per glucose molecule produced by substrate level phosphorylation. The reduced form of NADH is also produced in this process. Glycolysis can occur in the presence or absence of oxygen.

3. Fermentation, which does not require oxygen, is the process by which the pyruvate of glycolysis is converted into various end products (e.g., lactic acid, ethanol, butanol), depending on the individual bacterial species. These organic end products serve as electron acceptors to recycle the NADH from glycolysis, to NAD, which is necessary to continue the glycolytic process.
Obligate aerobes are unable to use fermentative processes. Bacterial identification may be aided by the determination of fermentative end products (e.g., Lactobacillus, lactic acid; Saccharomyces, ethanol).

4. Respiration is an energy-producing, oxidative sequence of reactions in which inorganic compounds act as the final electron acceptor. This process includes glycolysis, the tricarboxylic
acid (TCA) cycle, and the electron transport system, which yields ATP when coupled with oxidative phosphorylation.
a. The tricarboxylic acid cycle further oxidizes the pyruvate produced from glycolysis and generates a substantial number of NADH (and FADH2), which yield ATP through the electron transport chain.
b. In the electron transport chain, which is located in the cytoplasmic membrane of bacteria,
as opposed to the mitochondrial membrane of eukaryotes, electrons carried by NADH (or FADH2) are passed through a series of donor–acceptor pairs (cytochromes, flavoproteins, and ubiquinones) and ultimately to a final electron acceptor, either oxygen (aerobic respiration) or another inorganic acceptor (anaerobic respiration) (e.g., nitrate, sulfate, carbon dioxide, ferric iron). Anaerobic organisms are less efficient at energy production than aerobic organisms, although anaerobic respiration is more efficient than fermentation alone.

5. Catabolism of proteins, polysaccharides, and lipids produces glucose, pyruvate, lipids, or other intermediates of the TCA cycle, which can then be directed toward energy production by entering the TCA cycle at various points.

E. Genetics
1. The genome of a typical bacterium consists of a single, circular DNA molecule (chromosome).Bacteria are haploid (Haploid is the term used when a cell has only one set of chromosomes.) in that they have a single chromosome and therefore a single copy of each gene.

2. Regulation and expression of genetic information
a. DNA has many functions.
(1) It is duplicated for transfer to progeny (a new organism produced by one or more parents) during cell division.
(2) It is transcribed into RNA, which can be translated into proteins.
(3) It can be mutated to alter specific characteristics encoded by genes.
(4) It can be duplicated and transferred to other bacterial cells in processes other than cell
division.
b. DNA replication, transcription, and translation
(1) Bacterial replication involves accurate duplication of chromosomal DNA, which enables the formation of two identical daughter cells. Replication is initiated at a specific sequence in the chromosome (origin) and involves a number of enzymes. The two DNA strands unwind as the replication fork progresses, synthesizing new DNA, bidirectionally, with the original DNA strands serving as templates.

(2) Transcription is the process by which the DNA sequence is copied into an RNA molecule that will then be used to produce necessary proteins. One gene can be transcribed into many copies of RNA. Simplistically, sigma factors bind to the promoter region of the gene and provide a docking site for the RNA polymerase. The area undergoes localized unwinding to allow RNA polymerase to transcribe the RNA (called mRNA) from the DNA template. The RNA is not processed, as in eukaryotes; there are no introns and exons; no capping of the beginning of the transcript (the 59 end); and no polyadenine tails added to the terminus (the 39 end) of the mRNA transcript.

(3) Translation is the process of converting the genetic information contained in the mRNA into an amino acid sequence. As the transcript is being made, the 70S bacterial ribosome assembles at the 59 end of the transcript with the transfer RNA (tRNA) for formylmethionine (fmet) at the start codon (AUG) of the mRNA. The ribosome contains two tRNA binding sites, each of which allows the codon of the mRNA to basepair with the anticodon of the incoming, corresponding tRNA. The amino acid of the first tRNA is transferred to the adjacent amino acid on the new tRNA at the next codon (transpeptidase reaction); the empty tRNA (uncharged tRNA) is released, and the ribosome shifts to the next codon. This continues until the complete amino acid sequence (protein) is synthesized.

3. Mechanisms of genetic change. In addition to mutation, microorganisms can change their genetic constitution by the transfer of genetic material from a donor cell to a recipient cell. Transferred DNA can be integrated into the recipient chromosome, usually via recombination between homologous segments (those DNA areas that have similar nucleotide sequences), or the DNA can be stably maintained as an extrachromosomal element (plasmid) or a bacterial virus (bacteriophage). Transposons are mobile genetic elements that, once they are inside of a bacterial cell, can transfer DNA within a cell, “hopping” from one place in the chromosome to another, or between the chromosome and a plasmid. Transposons carry the gene for the enzyme that mediates the insertion (transposase) and repeated sequence elements; transposons may also carry antibiotic resistance genes.

4. Exchange of bacterial genetic material can occur by three general mechanisms:
a. Transformation involves a recipient cell taking up cell-free, fragmented (i.e., naked) DNA.
(1) Transformation occurs naturally within only a few bacterial genera (e.g., Neisseria). Following uptake of the DNA, homologous recombination can incorporate the new sequences into the recipient genome.
(2) Transformation is also associated with recombinant DNA technology or cloning. In this process, the bacterial cell walls are made leaky by chemical treatment or by electrical stimulus (electroporation). Cloning involves splicing a gene into a plasmid DNA ( vector).
All vectors share several common characteristics:
(a) Typically small, well-characterized molecules of DNA.
(b) Contain at least one replicon and can be replicated within the host even when the vector contains foreign DNA.
(c) Code for a phenotypic trait that can be used to detect the presence of the foreign DNA, which can be used to distinguish parental from recombinant vectors.
(d) Selectable markers (e.g., antibiotic resistance) to find cells that contain these vectors. This marker confers a selective advantage for the bacterial host, such that the plasmid will be stably maintained.

b. Conjugation is the one-way transfer of DNA from a donor cell to a recipient cell through a sex pilus. Donor cells contain the F plasmid, which carries the genes for constructing the sex pilus and transferring the plasmid. Chromosomal DNA can transfer with the F plasmid in certain circumstances. If the F plasmid is integrated into the bacterial chromosome, the strain is designated Hfr (high-frequency recombination), which will transfer significantly more chromosomal DNA. see more

c. Transduction is the transfer of genetic material by bacteriophages. During an infection, the bacteriophage may package fragments of the host DNA into bacteriophage particles, which may then be carried into the recipient bacterial cell at the time of infection. Bacteriophage can result in a lytic infection in which the bacteriophage enters the cell, replicates, and lyses the cell to release new progeny bacteriophage. Lysogenic infections incorporate the phage genome into the bacterial host DNA. Upon lysogenic conversion, the recipient cell can acquire traits that were carried with the bacteriophage genome. Several toxins are encoded by bacteriophage, for example, Corynebacterium diphtheriae (diphtheria toxin), Streptococcus pyogenes (erythrogenic toxin in scarlet fever), and Clostridium tetani (tetanus toxin). The lysogenic (temperate) phage may remain as part of the bacterial genome or can convert to a lytic infection. Transduction is considered specialized if the packaged bacterial DNA was adjacent to the integration site for the phage or generalized if the transferred DNA originated from random host sequences.

F. Examples of unique bacteria
1. Chlamydiae (e.g., Chlamydia trachomatis, which causes blindness and sexually transmitted diseases) are obligate intracellular parasites that
a. lack the ability to generate ATP, which they must obtain from the host cell, and
b. have a two-phase life cycle.
(1) The infectious form, or elementary body (EB), is a dense, nonreplicating cell that is resistant to drying in the environment.
(2) The reticulate body (RB) forms from the EB after entry into the host cell. The RB is the metabolically active form that multiplies within the host cell vacuole. EBs form from the dividing RBs and will be liberated to infect new cells when the damaged host cell dies.

2. Human pathogens in the family Rickettsiaceae (Rickettsia, Ehrlichia) are obligate intracellular parasites, most of which are transmitted by arthropods (e.g., Rickettsia rickettsii, which causes Rocky Mountain spotted fever). They tend to invade endothelial cells, resulting in a rash, vasculitis, and fever.

3. Mycoplasmas, the smallest bacteria, are unique in that they lack a cell wall and are thus pleomorphic (Pleomorphism: variability in the size and shape of cells) in shape. Unlike other prokaryotic organisms, mycoplasma plasma membranes contain sterols (e.g., Mycoplasma pneumoniae, which causes an atypical or walking pneumonia).

G. Mechanisms of pathogenicity
1. Overview. Although signs and symptoms of bacterial disease are often the result of the host response, microorganisms can damage tissue through the production of exotoxins and endotoxins and by the direct effects of the microbe growth.
a. Pathogens are microbes that have mechanisms (virulence factors) to promote invasion or
toxigenicity. The presence of these organisms is associated with disease.
b. Opportunists are microbes that take advantage of preexisting conditions (e.g., immunosuppression, injury, reduced normal flora, organ dysfunction) to enhance the ability of the microbe to cause disease.

2. Determinants of bacterial pathogenesis are those features or components of the microbe that allow it to associate with the host or cause disease; virulence factors are the characteristics of an organism that allow it to either damage the host or evade host defenses.

3. Mechanisms of disease
a. Exotoxins are polypeptides that are secreted by certain bacteria that alter specific host cell function (e.g., cholera toxin increases adenylate cyclase activity, leading to loss of fluid and electrolytes; diphtheria toxin prevents protein synthesis by the ribosome, resulting in cell death). They may be produced by gram-positive and gram-negative bacteria.
(1) Exotoxins secreted into food or water that are then ingested by a host cause intoxication (e.g., botulism and staphylococcal food poisoning).
(2) Exotoxins produced during an infection may interfere with cell function or physically damage the cell (e.g., Bordetella pertussis, C. diphtheriae, V. cholerae).
(3) Exotoxins are antigenic; toxoids are exotoxins that have been modified (inactivated) to induce immunity without toxic effects.

b. Infection is sufficient to cause disease for some microorganisms, especially when the presence of the bacteria elicits a strong inflammatory response. Bacterial infections often elicit host immune responses that are pyogenic (pus producing), involving neutrophils (e.g., streptococcal pharyngitis, gonococcal urethritis), or granulomatous, which elicit macrophages and T-lymphocytes, resulting in an inflammatory lesion (granuloma) that can be important for diagnosis (e.g., tuberculosis). Rashes associated with many bacterial infections are often due to inflammation elicited by the presence of the bacteria (e.g., Rocky Mountain spotted fever, meningococcemia (Meningococcemia is defined as dissemination of meningococci (Neisseria meningitidis) into the bloodstream) ). In some cases, infection may be followed by toxin production, as in diphtheria.

c. Invasion of host tissues and then growth in the tissue is often facilitated by bacterial enzymes (e.g., hyaluronidase, IgA protease, and hemolysin), which act on host tissues and immune defenses. Intracellular bacteria invade host cells to avoid immune responses (e.g., Mycobacterium, Shigella, and Listeria). Some bacteria (e.g., Shigella species, Clostridium perfringens) are able to produce toxins after the invasion of host tissue.

Ref:

http://textbookofbacteriology.net/bacteriology_2.html
http://www.invivogen.com/review-mycoplasma
http://emedicine.medscape.com/article/221473-overview

Comprehensive Pharmacy Review
Wikipedia

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