Gram-negative bacteria are a group of bacteria that do not retain the
crystal violet stain used in the gram-staining method of bacterial
differentiation. They are characterized by their cell envelopes,
which are composed of a thin peptidoglycan cell wall sandwiched
between an inner cytoplasmic cell membrane and a bacterial outer
Gram-negative bacteria are found everywhere, in virtually all
Earth that support life. The gram-negative bacteria
include the model organism Escherichia coli, as well as many
pathogenic bacteria, such as
Pseudomonas aeruginosa, Neisseria
gonorrhoeae, Chlamydia trachomatis, and Yersinia pestis. They are an
important medical challenge, as their outer membrane protects them
from many antibiotics (including penicillin); detergents that would
normally damage the peptidoglycans of the (inner) cell membrane; and
lysozyme, an antimicrobial enzyme produced by animals that forms part
of the innate immune system. Additionally, the outer leaflet of this
membrane comprises a complex lipopolysaccharide (LPS) whose lipid A
component can cause a toxic reaction when these bacteria are lysed by
immune cells. This toxic reaction can include fever, an increased
respiratory rate, and low blood pressure — a life-threatening
condition known as septic shock.
Several classes of antibiotics have been designed to target
gram-negative bacteria, including aminopenicillins, ureidopenicillins,
cephalosporins, beta-lactam-betalactamase combinations (e.g.
pipercillin-tazobactam), Folate antagonists, quinolones, and
carbapenems. Many of these antibiotics also cover gram positive
organisms. The drugs that specifically target gram negative organisms
include aminoglycosides, monobactams (aztreonam) and Ciprofloxacin.
3.1 Example species
4 Bacterial transformation
5 Medical treatment
6 Orthographic note
7 See also
9 External links
Gram-negative cell wall structure
Gram-positive and -negative bacteria are differentiated chiefly by
their cell wall structure
Gram-negative bacteria display these characteristics:
An inner cell membrane is present (cytoplasmic)
A thin peptidoglycan layer is present (This is much thicker in
Has outer membrane containing lipopolysaccharides (LPS, which consists
of lipid A, core polysaccharide, and O antigen) in its outer leaflet
and phospholipids in the inner leaflet
Porins exist in the outer membrane, which act like pores for
Between the outer membrane and the cytoplasmic membrane there is a
space filled with a concentrated gel-like substance called periplasm
S-layer is directly attached to the outer membrane rather than to
If present, flagella have four supporting rings instead of two
Teichoic acids or lipoteichoic acids are absent
Lipoproteins are attached to the polysaccharide backbone
Some contain Braun's lipoprotein, which serves as a link between the
outer membrane and the peptidoglycan chain by a covalent bond
Most, with very few exceptions, do not form spores
Along with cell shape, gram-staining is a rapid diagnostic tool and
once was used to group species at the subdivision of Bacteria.
Historically, the kingdom
Monera was divided into four divisions based
on gram-staining: Firmacutes (+), Gracillicutes (−),
and Mendocutes (var.). Since 1987, the monophyly of the
gram-negative bacteria has been disproven with molecular studies.
However some authors, such as
Cavalier-Smith still treat them as a
monophyletic taxon (though not a clade; his definition of monophyly
requires a single common ancestor but does not require holophyly, the
property that all descendents be encompassed by the taxon) and refer
to the group as a subkingdom "Negibacteria".
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Bacteria are traditionally divided into the two groups: gram-positive
and gram-negative, based on their gram-staining response.
Gram-positive bacteria are also referred to as monoderms having one
membrane, and gram-negative bacteria are also referred to as diderms,
having two membranes. These groups are often thought of as lineages,
with gram-negative bacteria more closely related to one another than
to gram-positive bacteria. While this is often true, the
classification system breaks down in some cases. A given bacteria's
staining result, bacterial membrane organization, and lineage
groupings do not always match up. Thus, gram-staining
cannot be reliably used to assess familial relationships of bacteria.
However, staining often gives reliable information about the
composition of the cell membrane, distinguishing between the presence
or absence of an outer lipid membrane.
Of these two structurally distinct groups of prokaryotic organisms,
monoderm prokaryotes are indicated to be ancestral. Based upon a
number of different observations including that the gram-positive
bacteria are the major reactors to antibiotics and that gram-negative
bacteria are, in general, resistant to them, it has been proposed that
the outer cell membrane in gram-negative bacteria (diderms) evolved as
a protective mechanism against antibiotic selection
pressure. Some bacteria such as Deinococcus, which stain
gram-positive due to the presence of a thick peptidoglycan layer, but
also possess an outer cell membrane are suggested as intermediates in
the transition between monoderm (gram-positive) and diderm
(gram-negative) bacteria. The diderm bacteria can also be
further differentiated between simple diderms lacking
lipopolysaccharide; the archetypical diderm bacteria, in which the
outer cell membrane contains lipopolysaccharide; and the diderm
bacteria, in which the outer cell membrane is made up of mycolic acid
(e. g. Mycobacterium).
In addition, a number of bacterial taxa (including Negativicutes,
Fusobacteria, Synergistetes, and Elusimicrobia) that are either part
of the phylum
Firmicutes or branches in its proximity are also found
to possess a diderm cell structure. However, a conserved
signature indel (CSI) in the
HSP60 (GroEL) protein distinguishes all
traditional phyla of gram-negative bacteria (e.g., Proteobacteria,
Aquificae, Chlamydiae, Bacteroidetes, Chlorobi, Cyanobacteria,
Fibrobacteres, Verrucomicrobia, Planctomycetes, Spirochetes,
Acidobacteria) from these other atypical diderm bacteria as well as
other phyla of monoderm bacteria (e.g., Actinobacteria, Firmicutes,
Thermotogae, Chloroflexi). The presence of this CSI in all
sequenced species of conventional lipopolysaccharide-containing
gram-negative bacterial phyla provides evidence that these phyla of
bacteria form a monophyletic clade and that no loss of the outer
membrane from any species from this group has occurred.
The proteobacteria are a major phylum of gram-negative bacteria,
Escherichia coli (E. coli), Salmonella, Shigella, and other
Enterobacteriaceae, Pseudomonas, Moraxella, Helicobacter,
Stenotrophomonas, Bdellovibrio, acetic acid bacteria,
Other notable groups of gram-negative bacteria include the
cyanobacteria, spirochaetes, green sulfur, and green non-sulfur
Medically relevant gram-negative cocci include the four types that
cause a sexually transmitted disease (Neisseria gonorrhoeae), a
meningitis (Neisseria meningitidis), and respiratory symptoms
(Moraxella catarrhalis, Haemophilus influenzae).
Medically relevant gram-negative bacilli include a multitude of
species. Some of them cause primarily respiratory problems (Klebsiella
Pseudomonas aeruginosa), primarily
urinary problems (Escherichia coli, Proteus mirabilis, Enterobacter
cloacae, Serratia marcescens), and primarily gastrointestinal problems
Gram-negative bacteria associated with hospital-acquired infections
include Acinetobacter baumannii, which cause bacteremia, secondary
meningitis, and ventilator-associated pneumonia in hospital
Transformation is one of three processes for horizontal gene transfer,
in which exogenous genetic material passes from bacterium to another,
the other two being conjugation (transfer of genetic material between
two bacterial cells in direct contact) and transduction (injection of
foreign DNA by a bacteriophage virus into the host bacterium). In
transformation, the genetic material passes through the intervening
medium, and uptake is completely dependent on the recipient
As of 2014 about 80 species of bacteria were known to be capable of
transformation, about evenly divided between
Gram-negative bacteria; the number might be an overestimate since
several of the reports are supported by single papers.
Transformation has been studied in medically important Gram-negative
bacteria species such as
Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae
and Vibrio cholerae. It has also been studied in gram-negative
species found in soil such as
Pseudomonas stutzeri, Acinetobacter
baylyi, and gram-negative plant pathogens such as Ralstonia
solanacearum and Xylella fastidiosa.
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One of the several unique characteristics of gram-negative bacteria is
the structure of the bacterial outer membrane. The outer leaflet of
this membrane comprises a complex lipopolysaccharide (LPS) whose lipid
portion acts as an endotoxin. If gram-negative bacteria enter the
circulatory system, the liposaccharide can cause a toxic reaction.
This results in fever, an increased respiratory rate, and low blood
pressure. This may lead to life-threatening septic shock.
The outer membrane protects the bacteria from several antibiotics,
dyes, and detergents that would normally damage either the inner
membrane or the cell wall (made of peptidoglycan). The outer membrane
provides these bacteria with resistance to lysozyme and penicillin.
The periplasmic space (space between the two cell membranes) also
contains enzymes which break down or modify antibiotics. Drugs
commonly used to treat gram negative infections include amino, carboxy
and ureido penicillins (ampicillin, amoxicillin, pipercillin,
ticarcillin) these drugs may be combined with beta-lactamase
inhibitors to combat the presence of enzymes that can digest these
drugs (known as beta-lactamases) in the peri-plasmic space. Other
classes of drugs that have gram negative spectrum include
cephalosporins, monobactams (aztreonam), aminogylosides, quinolones,
macrolides, chloramphenicol, folate antagonists, and carbapenems.
The pathogenic capability of gram-negative bacteria is often
associated with certain components of their membrane, in particular,
the LPS. In humans, the presence of LPS triggers an innate immune
response, activating the immune system and producing cytokines
Inflammation is a common reaction to cytokine
production, which can also produce host toxicity. The innate immune
response to LPS, however, is not synonymous with pathogenicity, or the
ability to cause disease.
Gram-positive and Gram-negative derive from the surname
of Hans Christian Gram, a Danish bacteriologist; as eponymous
adjectives, their initial letter can be either capital G or lower-case
g, depending on which style guide (e.g., that of the CDC), if any,
governs the document being written. This is further explained at
Gram staining § Orthographic note.
Outer membrane receptor
This article incorporates public domain material from the
NCBI document "Science Primer".
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3D structures of proteins from inner membranes of Ellie Wyithe's
Vaginal (In pregnancy)
Primary nutritional groups
Bacterial cellular morphologies
Cell wall: Peptidoglycan
Gram-positive bacteria only: Teichoic acid
Gram-negative bacteria only: Bacterial outer membrane
Mycobacteria only: Arabinogalactan
Former groupings: Schizomycetes
Bacteria classification (phyla and orders)
Source: Bergey's Manual (2001–2012). Alternative views: Wikispecies.