Gram-negative bacteria

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Microscopic image of gram-negative Pseudomonas aeruginosa bacteria (pink-red rods) Pseudomonas aeruginosa Gram.jpg
Microscopic image of gram-negative Pseudomonas aeruginosa bacteria (pink-red rods)

Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. [1] Their defining characteristic is their cell envelope, which consists of a thin peptidoglycan cell wall sandwiched between an inner (cytoplasmic) membrane and an outer membrane. [2] These bacteria are found in all environments that support life on Earth.

Contents

Within this category, notable species include the model organism Escherichia coli , along with various pathogenic bacteria, such as Pseudomonas aeruginosa , Chlamydia trachomatis , and Yersinia pestis . They pose significant challenges in the medical field due to their outer membrane, which acts as a protective barrier against numerous antibiotics (including penicillin), detergents that would normally damage the inner cell membrane, and the antimicrobial enzyme lysozyme produced by animals as part of their innate immune system. Furthermore, the outer leaflet of this membrane contains a complex lipopolysaccharide (LPS) whose lipid A component can trigger a toxic reaction when the bacteria are lysed by immune cells. This reaction may lead to septic shock, resulting in low blood pressure, respiratory failure, reduced oxygen delivery, and lactic acidosis. [3]

Several classes of antibiotics have been developed to target gram-negative bacteria, including aminopenicillins, ureidopenicillins, cephalosporins, beta-lactam-betalactamase inhibitor combinations (such as piperacillin-tazobactam), folate antagonists, quinolones, and carbapenems. Many of these antibiotics also cover gram-positive bacteria. The antibiotics that specifically target gram-negative organisms include aminoglycosides, monobactams (such as aztreonam), and ciprofloxacin.

Characteristics

Gram-negative cell wall structure Gram negative cell wall.svg
Gram-negative cell wall structure
Gram-positive and -negative bacteria are differentiated chiefly by their cell wall structure Gram-Cell-wall.svg
Gram-positive and -negative bacteria are differentiated chiefly by their cell wall structure

Conventional gram-negative (LPS-diderm) bacteria display the following characteristics:[ citation needed ]

Classification

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: Firmicutes (+), Gracillicutes (−), Mollicutes (0) and Mendocutes (var.). [4] Since 1987, the monophyly of the gram-negative bacteria has been disproven with molecular studies. [5] 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 descendants be encompassed by the taxon) and refer to the group as a subkingdom "Negibacteria". [6]

Taxonomy

Bacteria are traditionally classified based on their Gram-staining response into the gram-positive and gram-negative bacteria. Having just one membrane, the gram-positive bacteria are also known as monoderm bacteria, while gram-negative bacteria, having two membranes, are also known as diderm bacteria. It was traditionally thought that the groups represent lineages, i.e., the extra membrane only evolved once, such that gram-negative bacteria are more closely related to one another than to any gram-positive bacteria. While this is often true, the classification system breaks down in some cases, with lineage groupings not matching the staining result. [7] [8] [9] [10] Thus, Gram staining cannot be reliably used to assess familial relationships of bacteria. Nevertheless, staining often gives reliable information about the composition of the cell membrane, distinguishing between the presence or absence of an outer lipid membrane. [7] [11]

Of these two structurally distinct groups of prokaryotic organisms, monoderm prokaryotes are thought to be ancestral. Based upon a number of different observations, including that the gram-positive bacteria are the most sensitive to antibiotics and that the gram-negative bacteria are, in general, resistant to antibiotics, it has been proposed that the outer cell membrane in gram-negative bacteria (diderms) evolved as a protective mechanism against antibiotic selection pressure. [7] [8] [11] [12] 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. [7] [12] The diderm bacteria can also be further differentiated between simple diderms lacking lipopolysaccharide (LPS); 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 ). [9] [10] [12] [13]

The conventional LPS-diderm group of gram-negative bacteria (e.g., Pseudomonadota, Aquificota, Chlamydiota, Bacteroidota, Chlorobiota, "Cyanobacteria", Fibrobacterota, Verrucomicrobiota, Planctomycetota, Spirochaetota, Acidobacteriota; "Hydrobacteria") are uniquely identified by a few conserved signature indel (CSI) in the HSP60 (GroEL) protein. In addition, a number of bacterial taxa (including Negativicutes, Fusobacteriota, Synergistota, and Elusimicrobiota) that are either part of the phylum Bacillota (a monoderm group) or branches in its proximity are also found to possess a diderm cell structure. [10] [12] [13] They lack the GroEL signature. [12] 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. [12]

Example species

The proteobacteria are a major superphylum of gram-negative bacteria, including E. coli , Salmonella , Shigella , and other Enterobacteriaceae, Pseudomonas , Moraxella , Helicobacter , Stenotrophomonas , Bdellovibrio , acetic acid bacteria, Legionella etc. Other notable groups of gram-negative bacteria include the cyanobacteria, spirochaetes, green sulfur, and green non-sulfur bacteria [14] .[ citation needed ]

Medically-relevant gram-negative diplococci include the four types that cause a sexually transmitted disease ( Neisseria gonorrhoeae [15] ), a meningitis ( Neisseria meningitidis [16] ), and respiratory symptoms ( Moraxella catarrhalis , [17] A coccobacillus Haemophilus influenzae is another medically relevant coccal type. [18]

Medically relevant gram-negative bacilli include a multitude of species. Some of them cause primarily respiratory problems ( Klebsiella pneumoniae , Legionella pneumophila , Pseudomonas aeruginosa ), primarily urinary problems ( Escherichia coli , Proteus mirabilis , Enterobacter cloacae , Serratia marcescens ), and primarily gastrointestinal problems ( Helicobacter pylori , Salmonella enteritidis , Salmonella typhi ).[ citation needed ]

Gram-negative bacteria associated with hospital-acquired infections include Acinetobacter baumannii , which cause bacteremia, secondary meningitis, and ventilator-associated pneumonia in hospital intensive-care units.

Bacterial transformation

Transformation is one of three processes for horizontal gene transfer, in which exogenous genetic material passes from one 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). [19] [20] In transformation, the genetic material passes through the intervening medium, and uptake is completely dependent on the recipient bacterium. [19]

As of 2014 about 80 species of bacteria were known to be capable of transformation, about evenly divided between gram-positive and gram-negative bacteria; the number might be an overestimate since several of the reports are supported by single papers. [19] Transformation has been studied in medically important gram-negative bacteria species such as Helicobacter pylori , Legionella pneumophila , Neisseria meningitidis , Neisseria gonorrhoeae , Haemophilus influenzae and Vibrio cholerae . [21] 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 . [21]

Role in disease

Example of a workup algorithm of possible bacterial infection in cases with no specifically requested targets (non-bacteria, mycobacteria etc.), with most common situations and agents seen in a New England setting. Clinically significant Gram-negative bacteria are usually rods, as shown near bottom right. Although some gram-negative bacteria can be recognized by "bench tests", diagnosis in the modern microbiology lab usually involves MALDI-TOF and/or multitarget assay. Diagnostic algorithm of possible bacterial infection.png
Example of a workup algorithm of possible bacterial infection in cases with no specifically requested targets (non-bacteria, mycobacteria etc.), with most common situations and agents seen in a New England setting. Clinically significant Gram-negative bacteria are usually rods, as shown near bottom right. Although some gram-negative bacteria can be recognized by "bench tests", diagnosis in the modern microbiology lab usually involves MALDI-TOF and/or multitarget assay.

One of the several unique characteristics of gram-negative bacteria is the structure of the bacterial outer membrane. The outer leaflet of this membrane contains lipopolysaccharide (LPS), whose lipid A portion acts as an endotoxin. [1] If gram-negative bacteria enter the circulatory system, LPS can trigger an innate immune response, activating the immune system and producing cytokines (hormonal regulators). This leads to inflammation and can cause a toxic reaction, resulting in fever, an increased respiratory rate, and low blood pressure. That is why some infections with gram-negative bacteria can lead to life-threatening septic shock. [3]

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), aminoglycosides, quinolones, macrolides, chloramphenicol, folate antagonists, and carbapenems. [22]

Orthographic note

The adjectives 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. [23] This is further explained at Gram staining § Orthographic note .

See also

Related Research Articles

<span class="mw-page-title-main">Gram stain</span> Investigative procedure in microbiology

Gram stain, is a method of staining used to classify bacterial species into two large groups: gram-positive bacteria and gram-negative bacteria. It may also be used to diagnose a fungal infection. The name comes from the Danish bacteriologist Hans Christian Gram, who developed the technique in 1884.

<span class="mw-page-title-main">Gram-positive bacteria</span> Bacteria that give a positive result in the Gram stain test

In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall.

Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like layer (sacculus) that surrounds the bacterial cytoplasmic membrane. The sugar component consists of alternating residues of β-(1,4) linked N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM). Attached to the N-acetylmuramic acid is an oligopeptide chain made of three to five amino acids. The peptide chain can be cross-linked to the peptide chain of another strand forming the 3D mesh-like layer. Peptidoglycan serves a structural role in the bacterial cell wall, giving structural strength, as well as counteracting the osmotic pressure of the cytoplasm. This repetitive linking results in a dense peptidoglycan layer which is critical for maintaining cell form and withstanding high osmotic pressures, and it is regularly replaced by peptidoglycan production. Peptidoglycan hydrolysis and synthesis are two processes that must occur in order for cells to grow and multiply, a technique carried out in three stages: clipping of current material, insertion of new material, and re-crosslinking of existing material to new material.

<span class="mw-page-title-main">Lipopolysaccharide</span> Class of molecules found in the outer membrane of gram-negative bacteria

Lipopolysaccharide, now more commonly known as endotoxin, is a collective term for components of the outermost membrane of cell envelope of gram-negative bacteria, such as E. coli and Salmonella with a common structural architecture. Lipopolysaccharides (LPS) are large molecules consisting of three parts: an outer core polysaccharide termed the O-antigen, an inner core oligosaccharide and Lipid A, all covalently linked. In current terminology, the term endotoxin is often used synonymously with LPS, although there are a few endotoxins that are not related to LPS, such as the so-called delta endotoxin proteins produced by Bacillus thuringiensis.

The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the periplasmic space in Gram-negative bacteria. Using cryo-electron microscopy it has been found that a much smaller periplasmic space is also present in Gram-positive bacteria, between cell wall and the plasma membrane. The periplasm may constitute up to 40% of the total cell volume of gram-negative bacteria, but is a much smaller percentage in gram-positive bacteria.

The cell envelope comprises the inner cell membrane and the cell wall of a bacterium. In Gram-negative bacteria an outer membrane is also included. This envelope is not present in the Mollicutes where the cell wall is absent.

<span class="mw-page-title-main">Polymyxin</span> Group of antibiotics

Polymyxins are antibiotics. Polymyxins B and E are used in the treatment of Gram-negative bacterial infections. They work mostly by breaking up the bacterial cell membrane. They are part of a broader class of molecules called nonribosomal peptides.

<span class="mw-page-title-main">Bacterial capsule</span> Polysaccharide layer that lies outside the cell envelope in many bacteria

The bacterial capsule is a large structure common to many bacteria. It is a polysaccharide layer that lies outside the cell envelope, and is thus deemed part of the outer envelope of a bacterial cell. It is a well-organized layer, not easily washed off, and it can be the cause of various diseases.

<i>Moraxella catarrhalis</i> Species of bacterium

Moraxella catarrhalis is a fastidious, nonmotile, Gram-negative, aerobic, oxidase-positive diplococcus that can cause infections of the respiratory system, middle ear, eye, central nervous system, and joints of humans. It causes the infection of the host cell by sticking to the host cell using trimeric autotransporter adhesins.

<span class="mw-page-title-main">Bacterial outer membrane</span> Plasma membrane found in gram-negative bacteria

The bacterial outer membrane is found in gram-negative bacteria. Gram-negative bacteria form two lipid bilayers in their cell envelopes - an inner membrane (IM) that encapsulates the cytoplasm, and an outer membrane (OM) that encapsulates the periplasm.

A bacterium, despite its simplicity, contains a well-developed cell structure which is responsible for some of its unique biological structures and pathogenicity. Many structural features are unique to bacteria and are not found among archaea or eukaryotes. Because of the simplicity of bacteria relative to larger organisms and the ease with which they can be manipulated experimentally, the cell structure of bacteria has been well studied, revealing many biochemical principles that have been subsequently applied to other organisms.

<span class="mw-page-title-main">Pathogenic bacteria</span> Disease-causing bacteria

Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often beneficial but others can cause infectious diseases. The number of these pathogenic species in humans is estimated to be fewer than a hundred. By contrast, several thousand species are part of the gut flora present in the digestive tract.

<span class="mw-page-title-main">Bacterial cellular morphologies</span> Shapes characteristic of certain bacteria and archaea

Bacterial cellular morphologies are the shapes that are characteristic of various types of bacteria and often key to their identification. Their direct examination under a light microscope enables the classification of these bacteria.

The Negativicutes are a class of bacteria in the phylum Bacillota, whose members have a peculiar cell wall with a lipopolysaccharide outer membrane which stains gram-negative, unlike most other members of the Bacillota. Although several neighbouring Clostridia species also stain gram-negative, the proteins responsible for the unusual diderm structure of the Negativicutes may have actually been laterally acquired from Pseudomonadota. Additional research is required to confirm the origin of the diderm cell envelope in the Negativicutes.

There are several models of the Branching order of bacterial phyla, one of these was proposed in 2001 by Gupta based on conserved indels or protein, termed "protein signatures", an alternative approach to molecular phylogeny. Some problematic exceptions and conflicts are present to these conserved indels, however, they are in agreement with several groupings of classes and phyla. One feature of the cladogram obtained with this method is the clustering of cell wall morphology from monoderms to transitional diderms to traditional diderms.

Bacterial morphological plasticity refers to changes in the shape and size that bacterial cells undergo when they encounter stressful environments. Although bacteria have evolved complex molecular strategies to maintain their shape, many are able to alter their shape as a survival strategy in response to protist predators, antibiotics, the immune response, and other threats.

<span class="mw-page-title-main">Trimeric autotransporter adhesin</span> Proteins found on the outer membrane of Gram-negative bacteria

In molecular biology, trimeric autotransporter adhesins (TAAs), are proteins found on the outer membrane of Gram-negative bacteria. Bacteria use TAAs in order to infect their host cells via a process called cell adhesion. TAAs also go by another name, oligomeric coiled-coil adhesins, which is shortened to OCAs. In essence, they are virulence factors, factors that make the bacteria harmful and infective to the host organism.

<span class="mw-page-title-main">Outer membrane vesicle</span> Vesicles released from the outer membranes of Gram-negative bacteria

Outer membrane vesicles (OMVs) are vesicles released from the outer membranes of Gram-negative bacteria. While Gram-positive bacteria release vesicles as well, those vesicles fall under the broader category of bacterial membrane vesicles (MVs). OMVs were the first MVs to be discovered, and are distinguished from outer inner membrane vesicles (OIMVs), which are gram-negative bacterial vesicles containing portions of both the outer and inner bacterial membrane. Outer membrane vesicles were first discovered and characterized using transmission-electron microscopy by Indian Scientist Prof. Smriti Narayan Chatterjee and J. Das in 1966-67. OMVs are ascribed the functionality to provide a manner to communicate among themselves, with other microorganisms in their environment and with the host. These vesicles are involved in trafficking bacterial cell signaling biochemicals, which may include DNA, RNA, proteins, endotoxins and allied virulence molecules. This communication happens in microbial cultures in oceans, inside animals, plants and even inside the human body.

<span class="mw-page-title-main">OBPgp279</span>

OBPgp279 is an endolysin that hydrolyzes peptidoglycan, a major constituent in bacterial membrane. OBPgp279 is found in Pseudomonas fluorescens phage OBP, which belongs in the Myoviridae family of bacteriophages. Because of its role in hydrolyzing the peptidoglycan layer, OBPgp279 is a key enzyme in the lytic cycle of the OBP bacteriophage; it allows the bacteriophage to lyse its host internally to escape. Unlike other endolysins, OBPgp279 does not rely on holins to perforate the inner bacterial membrane in order to reach the peptidoglycan layer. Although OBPgp279 is not a well-studied enzyme, it has garnered interest as a potential antibacterial protein due to its activity against multidrug-resistant gram-negative bacteria.

<span class="mw-page-title-main">Bacterial secretion system</span> Protein complexes present on the cell membranes of bacteria for secretion of substances

Bacterial secretion systems are protein complexes present on the cell membranes of bacteria for secretion of substances. Specifically, they are the cellular devices used by pathogenic bacteria to secrete their virulence factors to invade the host cells. They can be classified into different types based on their specific structure, composition and activity. Generally, proteins can be secreted through two different processes. One process is a one-step mechanism in which proteins from the cytoplasm of bacteria are transported and delivered directly through the cell membrane into the host cell. Another involves a two-step activity in which the proteins are first transported out of the inner cell membrane, then deposited in the periplasm, and finally through the outer cell membrane into the host cell.

References

Notes

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  2. ↑ Silhavy, T. J.; Kahne, D.; Walker, S. (2010-05-01). "The Bacterial Cell Envelope". Cold Spring Harbor Perspectives in Biology. 2 (5): a000414. doi:10.1101/cshperspect.a000414. ISSN   1943-0264. PMC   2857177 . PMID   20452953.
  3. 1 2 Pelletier, Lawrence L. (1996). "Microbiology of the Circulatory System". In Baron S (ed.). Medical Microbiology (4th ed.). University of Texas Medical Branch at Galveston. ISBN   978-0-9631172-1-2. PMID   21413321. Archived from the original on 2022-04-13. Retrieved 2021-05-12.
  4. ↑ Gibbons, N. E.; Murray, R. G. E. (1978). "Proposals Concerning the Higher Taxa of Bacteria". International Journal of Systematic Bacteriology. 28 (1): 1–6. doi: 10.1099/00207713-28-1-1 .
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  7. 1 2 3 4 Gupta, RS (December 1998). "Protein phylogenies and signature sequences: A reappraisal of evolutionary relationships among archaebacteria, eubacteria, and eukaryotes". Microbiol. Mol. Biol. Rev. 62 (4): 1435–91. doi:10.1128/MMBR.62.4.1435-1491.1998. PMC   98952 . PMID   9841678.
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  12. 1 2 3 4 5 6 Gupta RS (August 2011). "Origin of diderm (gram-negative) bacteria: antibiotic selection pressure rather than endosymbiosis likely led to the evolution of bacterial cells with two membranes". Antonie van Leeuwenhoek. 100 (2): 171–82. doi:10.1007/s10482-011-9616-8. PMC   3133647 . PMID   21717204.
  13. 1 2 Marchandin H, Teyssier C, Campos J, Jean-Pierre H, Roger F, Gay B, Carlier JP, Jumas-Bilak E (June 2010). "Negativicoccus succinicivorans gen. nov., sp. nov., isolated from human clinical samples, emended description of the family Veillonellaceae and description of Negativicutes classis nov., Selenomonadales ord. nov. and Acidaminococcaceae fam. nov. in the bacterial phylum Firmicutes". Int. J. Syst. Evol. Microbiol. 60 (Pt 6): 1271–9. doi: 10.1099/ijs.0.013102-0 . PMID   19667386.
  14. ↑ Guentzel, M. Neal (1996), Baron, Samuel (ed.), "Escherichia, Klebsiella, Enterobacter, Serratia, Citrobacter, and Proteus", Medical Microbiology (4th ed.), Galveston (TX): University of Texas Medical Branch at Galveston, ISBN   978-0-9631172-1-2, PMID   21413290 , retrieved 2024-03-28
  15. ↑ Yeshanew, Addisu Gize; Geremew, Rozina Ambachew (2018-07-17). "MNeisseria Gonorrhoae and their antimicrobial susceptibility patterns among symptomatic patients from Gondar town, north West Ethiopia". Antimicrobial Resistance and Infection Control. 7 (85): 85. doi: 10.1186/s13756-018-0376-3 . PMC   6050735 . PMID   30026943.
  16. ↑ "Vaccine Preventable Diseases Surveillance Manual". CDC. April 3, 2018. Retrieved January 26, 2024.
  17. ↑ Verduin, Cees M.; Hol, Cees; Fleer, Andre; van Dijk, Hans; van Belkum, Alex (January 2002). "Moraxella catarrhalis: from Emerging to Established Pathogen". Clinical Microbiology Reviews. 15 (1): 125–144. doi:10.1128/CMR.15.1.125-144.2002. PMC   118065 . PMID   11781271.
  18. ↑ "For Clinicians: Haemophilus influenzae". CDC. February 13, 2018. Retrieved January 26, 2024.
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  20. ↑ Korotetskiy I, Shilov S, Kuznetsova T, Kerimzhanova B, Korotetskaya N, Ivanova L, Zubenko N, Parenova R, Reva O (2023). "Analysis of Whole-Genome Sequences of Pathogenic Gram-Positive and Gram-Negative Isolates from the Same Hospital Environment to Investigate Common Evolutionary Trends Associated with Horizontal Gene Exchange, Mutations and DNA Methylation Patterning". Microorganisms. 11 (2): 323. doi: 10.3390/microorganisms11020323 . PMC   9961978 . PMID   36838287.
  21. 1 2 Seitz P, Blokesch M (2013). "Cues and regulatory pathways involved in natural competence and transformation in pathogenic and environmental Gram-negative bacteria". FEMS Microbiol. Rev. 37 (3): 336–63. doi: 10.1111/j.1574-6976.2012.00353.x . PMID   22928673.
  22. ↑ Glück, Thomas (12 December 2003). "Gram-Negative Bacteria and Broad-Spectrum Antibiotics: Good News Except for Fluoroquinolones". www.jwatch.org. NEJM Journal Watch. Archived from the original on 10 March 2018. Retrieved 10 March 2018.
  23. ↑ "Preferred Usage - Emerging Infectious Disease journal - CDC". CDC.gov. Centers for Disease Control and Prevention. Archived from the original on 2018-01-29. Retrieved 2018-03-04.
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