Background – Bacterial Strains:

1] General background comments- (bacteria)
2] Endospores
3] Classification (bacteria)
4] Associations (bacteria)
5] Extended-spectrum beta-lactamase (ESBL)
6] Carbapenem-resistant enterobacteriaceae (CRE)



  • The study of bacteria is known as bacteriology, a branch of microbiology.
  • Constitute a large domain or kingdom of prokaryotic microorganisms.  Prokaryotes:  Unlike cells of animals and other eukaryotes, bacterial cells do not contain a nucleus and rarely harbour membrane-bound organelles.
  • Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres (cocci)  to rods (bacilli) and spirals.  Bacteria display a wide diversity of shapes and sizes, called morphologies. Bacterial cells are about one-tenth the size of eukaryotic cells and are typically 0.5 – 5.0 micrometres in length.  Among the smallest bacteria are members of the genus Mycoplasma, which measure only 0.3 micrometers. Some bacteria, called vibrio, are shaped like slightly curved rods or comma-shaped; others can be spiral-shaped, called spirilla, or tightly coiled, called spirochetes.
  • Many bacterial species exist simply as single cells, others associate in characteristic patterns:
    • Neisseria form diploids (pairs),
    • Streptococcus form chains, and
    • Staphylococcus group together in “bunch of grapes” clusters.
    • Bacteria can also be elongated to form filaments, for example the Actinobacteria. Filamentous bacteria are often surrounded by a sheath that contains many individual cells.
    • Certain types, such as species of the genus Nocardia, even form complex, branched filaments, similar in appearance to fungal mycelia.
  • There are approximately ten times as many bacterial cells in the human flora as there are human cells in the body, with large numbers of bacteria on the skin and as gut flora.
  • The vast majority of the bacteria in the body are rendered harmless by the protective effects of the immune system, and some are beneficial. However, several species of bacteria are pathogenic and cause infectious diseases, including cholera, syphilis, anthrax, leprosy, and bubonic plague.
  • The most common fatal bacterial diseases are respiratory infections.
  • The bacterial cell is surrounded by a lipid membrane (also known as a cell membrane or plasma membrane). This membrane encloses the contents of the cell and acts as a barrier to hold nutrients, proteins and other essential components of the cytoplasm within the cell.  They lack a true nucleus, mitochondria, chloroplasts and the other organelles present in eukaryotic cells.
  • Most bacteria do not have a membrane-bound nucleus, and their genetic material is typically a single circular chromosome located in the cytoplasm in an irregularly shaped body called the nucleoid.
    • The nucleoid contains the chromosome with its associated proteins and RNA. Like all living organisms, bacteria contain ribosomes, often grouped in chains called polyribosomes, for the production of proteins, but the structure of the bacterial ribosome is different from that of eukaryotes and Archaea.
  • Bacterial ribosomes have a sedimentation rate of 70S: their subunits have rates of 30S and 50S. Some antibiotics bind specifically to 70S ribosomes and inhibit bacterial protein synthesis. Those antibiotics kill bacteria without affecting the larger 80S ribosomes of eukaryotic cells and without harming the host.
  • In most bacteria, a cell wall is present on the outside of the cytoplasmic membrane. The plasma membrane and cell wall comprise the cell envelope. A common bacterial cell wall material is peptidoglycan, which is made from polysaccharide chains cross-linked by peptides containing D-amino acids.
  • There are broadly speaking two different types of cell wall in bacteria, called Gram-positive and Gram-negative. The names originate from the reaction of cells to the Gram stain, a test long-employed for the classification of bacterial species.[63]
    • Gram-positive bacteria possess a thick cell wall containing many layers of peptidoglycan and teichoic acids.
    • Gram-negative bacteria have a relatively thin cell wall consisting of a few layers of peptidoglycan surrounded by a second lipid membrane containing lipopolysaccharides and lipoproteins.
      • Lipopolysaccharides, also called endotoxins, are composed of polysaccharides and lipid A (responsible for much of the toxicity of Gram-negative bacteria).
    • Most bacteria have the Gram-negative cell wall, and only the Firmicutes and Actinobacteria (previously known as the low G+C and high G+C Gram-positive bacteria, respectively) have the alternative Gram-positive arrangement.
    • These differences in structure can produce differences in antibiotic susceptibility; for instance, vancomycin can kill only Gram-positive bacteria and is ineffective against Gram-negative pathogens, such as Haemophilus influenzae or Pseudomonas aeruginosa.
  • Acid-fast bacteria, like Mycobacteria, are resistant to decolorization by acids during staining procedures. The high mycolic acid content of Mycobacteria, is responsible for the staining pattern of poor absorption followed by high retention. The most common staining technique used to identify acid-fast bacteria is the Ziehl-Neelsen stain or acid-fast stain, in which the acid-fast bacilli are stained bright-red and stand out clearly against a blue background.
  • Endospores  Top Of Page
    Certain genera of Gram-positive bacteria can form highly resistant, dormant structures called endospores., such as:
    •  Bacillus,
    • Clostridium,
    • Sporohalobacter,
    • Anaerobacter, and
    • Heliobacterium,
  • Endospores show no detectable metabolism and can survive extreme physical and chemical stresses, such as high levels of UV light, gamma radiation, detergents, disinfectants, heat, freezing, pressure, and desiccation.
  • Endospore-forming bacteria can also cause disease: for example, anthrax can be contracted by the inhalation of Bacillus anthracis endospores, and contamination of deep puncture wounds with Clostridium tetani endospores causes tetanus.
  • Classification: Top Of Page
    • Bacteria can be classified on the basis of cell structure, cellular metabolism or on differences in cell components such as DNA, fatty acids, pigments, antigens and quinones.
    • Classification of bacteria is determined by publication in the International Journal of Systematic Bacteriology, and Bergey’s Manual of Systematic Bacteriology. The International Committee on Systematic Bacteriology (ICSB) maintains international rules for the naming of bacteria and taxonomic categories and for the ranking of them in the International Code of Nomenclature of Bacteria.
    • Gram stain – characterizes bacteria based on the structural characteristics of their cell walls.
      • The thick layers of peptidoglycan in the “Gram-positive” cell wall stain purple,
      • The thin “Gram-negative” cell wall appears pink.
    • By combining morphology and Gram-staining, most bacteria can be classified as belonging to one of four groups:
      • Gram-positive cocci,
      • Gram-positive bacilli,
      • Gram-negative cocci and
      • Gram-negative bacilli.
      • Some organisms are best identified by stains other than the Gram stain, particularly mycobacteria or Nocardia, which show acid-fastness on Ziehl-Neelsen or similar stains. Other organisms may need to be identified by their growth in special media, or by other techniques, such as serology.
    • Once a pathogenic organism has been isolated, it can be further characterized by its morphology, growth patterns such as (aerobic or anaerobic growth, patterns of hemolysis) and staining.
  • Associations Top Of Page
    Despite their apparent simplicity, bacteria can form complex associations with other organisms. These symbiotic associations can be divided into:
    • parasitism,
    • mutualism and
    • commensalism.

Extended-spectrum beta-lactamase (ESBL):   Top Of Page

  • Members of the family enterobacteriaceae commonly express plasmid-encoded β-lactamases (e.g., TEM-1, TEM-2, and SHV-1), which confer resistance to penicillins but not to expanded-spectrum cephalosporins.
  • In the mid-1980s, a new group of enzymes, the extended-spectrum b-lactamases (ESBLs), was detected.
  • ESBLs are beta-lactamases that hydrolyze extended-spectrum cephalosporins with an oxyimino side chain. These cephalosporins include cefotaxime, ceftriaxone, and ceftazidime, as well as the oxyimino-monobactam aztreonam. Thus ESBLs confer resistance to these antibiotics and related oxyimino-beta lactams.
  • In typical circumstances, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of ß-lactam antibiotics susceptible to hydrolysis by these enzymes.
  • An increasing number of ESBLs not of TEM or SHV lineage have recently been described.
  • The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited.
  • Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates.


Carbapenem-resistant enterobacteriaceae (CRE): Top Of Page

  • Family of gram-negative bacteria that are nearly immune to the carbapenem class of antibiotics, considered the “drug of last resort” for such infections.
  • Enterobacteriaceae are common commensals and infectious agents.
  • The bacteria kill up to half of patients getting bloodstream infections from them. Death rates of up to 50% can be seen in patients with CRE sepsis, a rate much higher than other resistant infections such as MRSA or Clostridium difficile.
  • First detected in a North Carolina hospital in 2001 (Since that time, it has been identified in health care facilities in 41 other states).
  • During just the first half of 2012, almost 200 hospitals and long-term acute care facilities treated at least one patient infected with these bacteria. CRE has become increasingly common.
  • Resistance within Klebsiella pnuemoniae alone increased from 0.6% in 2004 to 5.6% in
    • The first outbreak involving colistin-resistant carbapenem-resistant K. pneumoniae in the U.S. was discovered in Detroit, MI in 2009, involving three different healthcare institutions.
  • Study conducted in the Melbourne, Australia ICU demonstrated that handwashing stations were locations of environmental reservoirs for CRE bacteria.  They determined that the main reservoirs for these CRE-resistant bacteria were the ICU sinks, and that inappropriate cleaning methods accounted for the primary method of transmission from sink to sink. Furthermore, the environmental strains of the CRE bacteria were the same strains infecting the patients in the ICU, as determined from genetic analysis.
  • Risks
    • Thus far, CRE has been a primarily nosocomial infectious agent.
    • Currently, almost all CRE infections occur in people receiving significant medical care in hospitals, long-term acute care facilities, or nursing homes.
    • Independent risk factors for CRE infection include, but aren’t limited to, use of beta-lactam antibiotics and the use of mechanical ventilation.
    • Patients who have been diagnosed with diabetes have also been shown to be at an elevated risk for acquiring CRE. 
    • When compared to other hospitalized patients, those admitted from long-term acute care facilities have significantly higher incidence of colonization and infection rates. Another multicenter study found that over 30% of patients with recent exposure to LTAC were colonized or infected with carbapenem-resistant Enterobacteriaceae.
    • A patient susceptible to CRE transmission is more likely to be female, have a greater number of parenteral nutrition-days, and to have had a significant number of days breathing through a ventilator.
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