Cross-resistance

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Cross-resistance is when something develops resistance to several substances that have a similar mechanism of action. For example, if a certain type of bacteria develops resistance to one antibiotic, that bacteria will also have resistance to several other antibiotics that target the same protein or use the same route to get into the bacterium. A real example of cross-resistance occurred for nalidixic acid and ciprofloxacin, which are both quinolone antibiotics. When bacteria developed resistance to ciprofloxacin, they also developed resistance to nalidixic acid because both drugs inhibit topoisomerase, a key enzyme in DNA replication. [1] Due to cross-resistance, antimicrobial treatments like phage therapy can quickly lose their efficacy against bacteria. [2] This makes cross-resistance an important consideration in designing evolutionary therapies.

Contents

Definition

Cross-resistance is the idea is that the development of resistance to one substance subsequently leads to resistance to one or more substances that can be resisted in a similar manner. It occurs when resistance is provided against multiple compounds through one single mechanism, like an efflux pump. [3] This can keep concentrations of a toxic substance at low levels and can do so for multiple compounds. Increasing the activity of such a mechanism in response to one compound then also has a similar effect on the others. The precise definition of cross-resistance depends on the field of interest.

Pest management

In pest management, cross-resistance is defined as the development of resistance by pest populations to multiple pesticides within a chemical family. [4] Similar to the case of microbes, this may occur due to sharing binding target sites. For example, cadherin mutations may result in cross resistance in H. armigera to Cry1Aa and Cry1Ab. There also exists multiple resistance in which resistance to multiple pesticides occurs via different resistance mechanisms as opposed to the same mechanisms. [5]

Microorganisms

In another case it is defined as the resistance of a virus to a new drug as a result of previous exposure to another drug. [6] Or in the context of microbes, it is the resistance to multiple different antimicrobial agents as a result of a single molecular mechanism. [7]

Antibiotic resistance

Cross-resistance is highly involved in the widespread issue of antibiotic resistance; an area of clinical relevance. There is a continued increase in the development of multidrug resistance in bacteria. This is partially due to the widespread use of antimicrobial compounds in diverse environments. [8] But resistance to antibiotics can arise in multiple ways, not necessarily being the result of exposure to an antimicrobial compound.

Structural similarity

Cross-resistance can take place between compounds that are chemically similar, like antibiotics within similar and different classes. [9] That said, structural similarity is a weak predictor of antibiotic resistance, and does not predict antibiotic resistance at all when aminoglycosides are disregarded in the comparison. [10]

Target similarity

Cross resistance will most commonly occur due to target similarity. This is possible when antimicrobial agents have the same target, initiate cell death in a similar manner or have a similar route of access. An example is cross-resistance between antibiotics and disinfectants. Exposure to certain disinfectants can lead to the increased expression of genes that encode for efflux pumps that are able to maintain low levels of antibiotics. Thus, the same mechanism that is used to clear the disinfectant compound from the cell can also be used to clear antibiotics from the cell. [11] Another example is cross-resistance between antibiotics and metals. As mentioned before, compounds do not have to be similar in structure in order to lead to cross-resistance. It can also occur when the same mechanism is used to remove the compound from the cell. In the bacteria Listeria monocytogenes a multi-drug efflux transporter has been found that could export both metals and antibiotics. [12] [13] Experimental work has shown that exposure to zinc can lead to increased levels of bacterial resistance to antibiotics. [14] Several other studies have reported cross-resistance to various types of metals and antibiotics. These worked through several mechanisms, like drug efflux systems and disulphide bond formation systems. The possible implication of this is that not only the presence of antibacterial compounds can lead to the development of resistance against antibiotics, but also environmental factors like exposure to heavy metals. [3]

Collateral sensitivity

Collateral sensitivity occurs when developing multidrug resistance causes a bacteria to develop sensitivity to other drugs. Such developments can be exploited by researchers in effort to combat the harms created by cross resistance to commonly used antibiotics. [15] Increased sensitivity to an antibiotic means that a lower concentration of antibiotic can be used to achieve adequate growth inhibition. Collateral sensitivity and antibiotic resistance exist as a trade off, in which the benefits gained by antibiotic resistance are balanced by the risks introduced by collateral sensitivity. [16]

See also

Related Research Articles

<span class="mw-page-title-main">Antibiotic</span> Antimicrobial substance active against bacteria

An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the ones which cause the common cold or influenza. Drugs which inhibit growth of viruses are termed antiviral drugs or antivirals. Antibiotics are also not effective against fungi. Drugs which inhibit growth of fungi are called antifungal drugs.

<span class="mw-page-title-main">Antimicrobial resistance</span> Resistance of microbes to drugs directed against them

Antimicrobial resistance occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance to the point that one or more drugs used to fight them are no longer effective. Fungi evolve antifungal resistance, viruses evolve antiviral resistance, protozoa evolve antiprotozoal resistance, and bacteria evolve antibiotic resistance. Together all of these come under the umbrella of antimicrobial resistance.

<span class="mw-page-title-main">Drug resistance</span> Pathogen resistance to medications

Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is, resistance has evolved. Antimicrobial resistance and antineoplastic resistance challenge clinical care and drive research. When an organism is resistant to more than one drug, it is said to be multidrug-resistant.

An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals are used against fungi. They can also be classified according to their function. The use of antimicrobial medicines to treat infection is known as antimicrobial chemotherapy, while the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis.

Multiple drug resistance (MDR), multidrug resistance or multiresistance is antimicrobial resistance shown by a species of microorganism to at least one antimicrobial drug in three or more antimicrobial categories. Antimicrobial categories are classifications of antimicrobial agents based on their mode of action and specific to target organisms. The MDR types most threatening to public health are MDR bacteria that resist multiple antibiotics; other types include MDR viruses, parasites.

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

Lincosamides are a class of antibiotics, which include lincomycin, clindamycin, and pirlimycin.

<span class="mw-page-title-main">Tetracycline antibiotics</span> Type of broad-spectrum antibiotic

Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of Streptomyces bacteria or produced semi-synthetically from those isolated compounds. Tetracycline molecules comprise a linear fused tetracyclic nucleus to which a variety of functional groups are attached. Tetracyclines are named after their four ("tetra-") hydrocarbon rings ("-cycl-") derivation ("-ine"). They are defined as a subclass of polyketides, having an octahydrotetracene-2-carboxamide skeleton and are known as derivatives of polycyclic naphthacene carboxamide. While all tetracyclines have a common structure, they differ from each other by the presence of chloro, methyl, and hydroxyl groups. These modifications do not change their broad antibacterial activity, but do affect pharmacological properties such as half-life and binding to proteins in serum.

In microbiology, the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical, usually a drug, which prevents visible in vitro growth of bacteria or fungi. MIC testing is performed in both diagnostic and drug discovery laboratories.

<span class="mw-page-title-main">Efflux pump</span> Protein complexes that move compounds, generally toxic, out of bacterial cells

An efflux pump is an active transporter in cells that moves out unwanted material. Efflux pumps are an important component in bacteria in their ability to remove antibiotics. The efflux could also be the movement of heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters. All microorganisms, with a few exceptions, have highly conserved DNA sequences in their genome that encode efflux pumps. Efflux pumps actively move substances out of a microorganism, in a process known as active efflux, which is a vital part of xenobiotic metabolism. This active efflux mechanism is responsible for various types of resistance to bacterial pathogens within bacterial species - the most concerning being antibiotic resistance because microorganisms can have adapted efflux pumps to divert toxins out of the cytoplasm and into extracellular media.

<i>Acinetobacter baumannii</i> Species of bacterium

Acinetobacter baumannii is a typically short, almost round, rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans, affecting people with compromised immune systems, and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples, it is almost exclusively isolated from hospital environments. Although occasionally it has been found in environmental soil and water samples, its natural habitat is still not known.

<span class="mw-page-title-main">Polypeptide antibiotic</span> Class of antibiotics

Polypeptide antibiotics are a chemically diverse class of anti-infective and antitumor antibiotics containing non-protein polypeptide chains. Examples of this class include actinomycin, bacitracin, colistin, and polymyxin B. Actinomycin-D has found use in cancer chemotherapy. Most other polypeptide antibiotics are too toxic for systemic administration, but can safely be administered topically to the skin as an antiseptic for shallow cuts and abrasions.

Persister cells are subpopulations of cells that resist treatment, and become antimicrobial tolerant by changing to a state of dormancy or quiescence. Persister cells in their dormancy do not divide. The tolerance shown in persister cells differs from antimicrobial resistance in that the tolerance is not inherited and is reversible. When treatment has stopped the state of dormancy can be reversed and the cells can reactivate and multiply. Most persister cells are bacterial, and there are also fungal persister cells, yeast persister cells, and cancer persister cells that show tolerance for cancer drugs.

SmeT is a transcriptional repressor protein of 24.6 kDa, found in the pathogenic bacteria Stenotrophomonas maltophilia. SmeT is responsible for the regulation of the Multidrug Resistance (MDR) efflux pump, SmeDEF, that gives the bacteria resistance to several antibiotics including macrolides, TMP/SMX, tetracycline, chloramphenicol, quinolones and erythromycin. SmeT is encoded 223 bp upstream of SmeDEF, with just 56 base pairs between their transcription start sites and an overlapping region between the promoters. The production of the SmeT protein downregulates its own transcription, along with that of the efflux pump by sterically hindering the binding of RNA Polymerase to the DNA. SmeDEF was the first MDR pump discovered in the S. maltophilia species. The pump is named by its different parts: SmeE, the transporter itself that spans the plasma membrane, SmeF, the protein on the outer portion of the membrane, and SmeD, a membrane fusion protein. On general purpose media and no selectors, the genes for MDR pumps are typically not expressed, and the repressor is found bound to the DNA. In fact, mutations in SmeT that lead to overexpression of SmeDEF can pose fitness challenges to the bacteria. However, this overexpression has been identified in the bacterium and may pose a threat to our health.

<span class="mw-page-title-main">Plasmid-mediated resistance</span> Antibiotic resistance caused by a plasmid

Plasmid-mediated resistance is the transfer of antibiotic resistance genes which are carried on plasmids. Plasmids possess mechanisms that ensure their independent replication as well as those that regulate their replication number and guarantee stable inheritance during cell division. By the conjugation process, they can stimulate lateral transfer between bacteria from various genera and kingdoms. Numerous plasmids contain addiction-inducing systems that are typically based on toxin-antitoxin factors and capable of killing daughter cells that don't inherit the plasmid during cell division. Plasmids often carry multiple antibiotic resistance genes, contributing to the spread of multidrug-resistance (MDR). Antibiotic resistance mediated by MDR plasmids severely limits the treatment options for the infections caused by Gram-negative bacteria, especially family Enterobacteriaceae. The global spread of MDR plasmids has been enhanced by selective pressure from antimicrobial medications used in medical facilities and when raising animals for food.

<span class="mw-page-title-main">Antibiotic resistance in gonorrhea</span>

Neisseria gonorrhoeae, the bacterium that causes the sexually transmitted infection gonorrhea, has developed antibiotic resistance to many antibiotics. The bacteria was first identified in 1879.

Multidrug resistance pumps also known Multidrug efflux pumps are a type of efflux pump and P-glycoprotein. MDR pumps in the cell membrane extrudes many foreign substances out of the cells and some pumps can have a broad specificity. MDR pumps exist in animals, fungi, and bacteria and likely evolved as a defense mechanism against harmful substances. There are seven families of MDRs and are grouped by homology, energy source, and overall structure.

<span class="mw-page-title-main">Resistance-nodulation-cell division superfamily</span>

Resistance-nodulation-division (RND) family transporters are a category of bacterial efflux pumps, especially identified in Gram-negative bacteria and located in the cytoplasmic membrane, that actively transport substrates. The RND superfamily includes seven families: the heavy metal efflux (HME), the hydrophobe/amphiphile efflux-1, the nodulation factor exporter family (NFE), the SecDF protein-secretion accessory protein family, the hydrophobe/amphiphile efflux-2 family, the eukaryotic sterol homeostasis family, and the hydrophobe/amphiphile efflux-3 family. These RND systems are involved in maintaining homeostasis of the cell, removal of toxic compounds, and export of virulence determinants. They have a broad substrate spectrum and can lead to the diminished activity of unrelated drug classes if over-expressed. The first reports of drug resistant bacterial infections were reported in the 1940s after the first mass production of antibiotics. Most of the RND superfamily transport systems are made of large polypeptide chains. RND proteins exist primarily in gram-negative bacteria but can also be found in gram-positive bacteria, archaea, and eukaryotes.

ESKAPE is an acronym comprising the scientific names of six highly virulent and antibiotic resistant bacterial pathogens including: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. The acronym is sometimes extended to ESKAPEE to include Escherichia coli. This group of Gram-positive and Gram-negative bacteria can evade or 'escape' commonly used antibiotics due to their increasing multi-drug resistance (MDR). As a result, throughout the world, they are the major cause of life-threatening nosocomial or hospital-acquired infections in immunocompromised and critically ill patients who are most at risk. P. aeruginosa and S. aureus are some of the most ubiquitous pathogens in biofilms found in healthcare. P. aeruginosa is a Gram-negative, rod-shaped bacterium, commonly found in the gut flora, soil, and water that can be spread directly or indirectly to patients in healthcare settings. The pathogen can also be spread in other locations through contamination, including surfaces, equipment, and hands. The opportunistic pathogen can cause hospitalized patients to have infections in the lungs, blood, urinary tract, and in other body regions after surgery. S. aureus is a Gram-positive, cocci-shaped bacterium, residing in the environment and on the skin and nose of many healthy individuals. The bacterium can cause skin and bone infections, pneumonia, and other types of potentially serious infections if it enters the body. S. aureus has also gained resistance to many antibiotic treatments, making healing difficult. Because of natural and unnatural selective pressures and factors, antibiotic resistance in bacteria usually emerges through genetic mutation or acquires antibiotic-resistant genes (ARGs) through horizontal gene transfer - a genetic exchange process by which antibiotic resistance can spread.

<span class="mw-page-title-main">Multidrug-resistant bacteria</span>

Multidrug-resistant bacteria are bacteria that are resistant to three or more classes of antimicrobial drugs. MDR bacteria have seen an increase in prevalence in recent years and pose serious risks to public health. MDR bacteria can be broken into 3 main categories: Gram-positive, Gram-negative, and other (acid-stain). These bacteria employ various adaptations to avoid or mitigate the damage done by antimicrobials. With increased access to modern medicine there has been a sharp increase in the amount of antibiotics consumed. Given the abundant use of antibiotics there has been a considerable increase in the evolution of antimicrobial resistance factors, now outpacing the development of new antibiotics.

References

  1. ↑ Périchon, B. "Cross Resistance". ScienceDirect. Encyclopedia of Microbiology. Retrieved 26 July 2021.
  2. ↑ Wright, Rosanna (3 October 2018). "Cross-resistance is modular in bacteria-phage interactions". PLOS Biology. 16 (10): e2006057. doi: 10.1371/journal.pbio.2006057 . PMC   6188897 . PMID   30281587.
  3. 1 2 Pal, Chandan; Asiani, Karishma; Arya, Sankalp; Rensing, Christopher; Stekel, Dov J.; Larsson, D. G. Joakim; Hobman, Jon L. (2017-01-01), Poole, Robert K. (ed.), "Chapter Seven - Metal Resistance and Its Association With Antibiotic Resistance", Advances in Microbial Physiology, Microbiology of Metal Ions, 70, Academic Press: 261–313, doi:10.1016/bs.ampbs.2017.02.001, PMID   28528649
  4. ↑ Sarwar, Muhammad; Aslam, Roohi (2020-01-01), Awasthi, L. P. (ed.), "Chapter 23 - New advances in insect vector biology and virus epidemiology", Applied Plant Virology, Academic Press, pp. 301–311, doi:10.1016/b978-0-12-818654-1.00023-2, ISBN   978-0-12-818654-1, S2CID   219881317 , retrieved 2021-09-23
  5. ↑ Wu, Yidong (2014-01-01), Dhadialla, Tarlochan S.; Gill, Sarjeet S. (eds.), "Chapter Six - Detection and Mechanisms of Resistance Evolved in Insects to Cry Toxins from Bacillus thuringiensis", Advances in Insect Physiology, Insect Midgut and Insecticidal Proteins, vol. 47, Academic Press, pp. 297–342, doi:10.1016/B978-0-12-800197-4.00006-3 , retrieved 2022-12-07
  6. ↑ Locarnini, Stephen; Bowden, Scott (2010-08-01). "Drug Resistance in Antiviral Therapy". Clinics in Liver Disease. Chronic Hepatitis B: An Update. 14 (3): 439–459. doi:10.1016/j.cld.2010.05.004. ISSN   1089-3261. PMID   20638024.
  7. ↑ Colclough, Abigail; Corander, Jukka; Sheppard, Samuel K.; Bayliss, Sion C.; Vos, Michiel (2019-01-28). "Patterns of cross-resistance and collateral sensitivity between clinical antibiotics and natural antimicrobials". Evolutionary Applications . 12 (5). Wiley: 878–887. Bibcode:2019EvApp..12..878C. doi:10.1111/eva.12762. ISSN   1752-4571. PMC   6503891 . PMID   31080502.
  8. ↑ Anes, João; McCusker, Matthew P.; Fanning, Séamus; Martins, Marta (2015-06-10). "The ins and outs of RND efflux pumps in Escherichia coli". Frontiers in Microbiology . 6: 587. doi: 10.3389/fmicb.2015.00587 . PMC   4462101 . PMID   26113845.
  9. ↑ Sanders, C C; Sanders, W E; Goering, R V; Werner, V (1984). "Selection of multiple antibiotic resistance by quinolones, beta-lactams, and aminoglycosides with special reference to cross-resistance between unrelated drug classes". Antimicrobial Agents and Chemotherapy. 26 (6). American Society for Microbiology: 797–801. doi:10.1128/aac.26.6.797. ISSN   0066-4804. PMC   180026 . PMID   6098219.
  10. ↑ Lázár, Viktória; Nagy, István; Spohn, Réka; Csörgő, Bálint; Györkei, Ádám; Nyerges, Ákos; Horváth, Balázs; Vörös, Andrea; Busa-Fekete, Róbert; Hrtyan, Mónika; Bogos, Balázs; Méhi, Orsolya; Fekete, Gergely; Szappanos, Balázs; Kégl, Balázs (2014). "Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network". Nature Communications. 5: 4352. Bibcode:2014NatCo...5.4352L. doi:10.1038/ncomms5352. PMC   4102323 . PMID   25000950.
  11. ↑ Chapman, John S. (2003). "Disinfectant resistance mechanisms, cross-resistance, and co-resistance". International Biodeterioration & Biodegradation . Hygiene and Disinfection. 51 (4). Elsevier: 271–276. Bibcode:2003IBiBi..51..271C. doi:10.1016/s0964-8305(03)00044-1. ISSN   0964-8305.
  12. ↑ Mata, M.T.; Baquero, F.; Pérez-Díaz, J.C. (2000). "A multidrug efflux transporter in Listeria monocytogenes". FEMS Microbiology Letters. 187 (2): 185–188. doi: 10.1111/j.1574-6968.2000.tb09158.x . ISSN   0378-1097. PMID   10856655.
  13. ↑ Baker-Austin, Craig; Wright, Meredith S.; Stepanauskas, Ramunas; McArthur, J.V. (2006). "Co-selection of antibiotic and metal resistance". Trends in Microbiology . 14 (4). Cell Press: 176–182. doi:10.1016/j.tim.2006.02.006. ISSN   0966-842X. PMID   16537105.
  14. ↑ Peltier, Edward; Vincent, Joshua; Finn, Christopher; Graham, David W. (2010). "Zinc-induced antibiotic resistance in activated sludge bioreactors". Water Research . 44 (13). International Water Association (Elsevier): 3829–3836. Bibcode:2010WatRe..44.3829P. doi:10.1016/j.watres.2010.04.041. ISSN   0043-1354. PMID   20537675.
  15. ↑ Pál, Csaba; Papp, Balázs; Lázár, Viktória (July 2015). "Collateral sensitivity of antibiotic-resistant microbes". Trends in Microbiology. 23 (7): 401–407. doi:10.1016/j.tim.2015.02.009. ISSN   0966-842X. PMC   5958998 . PMID   25818802.
  16. ↑ Roemhild, Roderich; Andersson, Dan I. (2021-01-14). "Mechanisms and therapeutic potential of collateral sensitivity to antibiotics". PLOS Pathogens. 17 (1): e1009172. doi: 10.1371/journal.ppat.1009172 . ISSN   1553-7374. PMC   7808580 . PMID   33444399.
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