Editing Bacillus cereus (section)

==Pathogenesis==
''B.&nbsp;cereus'' is responsible for a minority of foodborne illnesses (2–5%), causing severe [[nausea]], [[vomiting]], and [[diarrhea]].<ref>{{cite journal | vauthors = Kotiranta A, Lounatmaa K, Haapasalo M | title = Epidemiology and pathogenesis of Bacillus cereus infections | journal = Microbes and Infection | volume = 2 | issue = 2 | pages = 189–198 | date = February 2000 | pmid = 10742691 | doi = 10.1016/S1286-4579(00)00269-0 }}</ref> ''Bacillus'' foodborne illnesses occur due to survival of the bacterial endospores when contaminated food is not, or is inadequately, cooked.<ref>{{cite book | vauthors = Turnbull PC |title=Baron's Medical Microbiology |publisher=University of Texas Medical Branch |year=1996 |isbn=978-0-9631172-1-2 | veditors = Baron S |edition=4th |chapter=''Bacillus'' |pmid=21413260 |display-editors=etal |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK7699/#939 |via=NCBI Bookshelf}}</ref> Cooking temperatures less than or equal to {{convert|100|C|F}} allow some ''B.&nbsp;cereus'' [[Endospore|spores]] to survive.<ref name="microorganisms.in.foods.p.242">{{cite book | vauthors = Roberts TA, Baird-Parker AC, Tompkin RB |url= https://books.google.com/books?id=lxycHnaPfCYC&pg=PA24 |title=Characteristics of Microbial Pathogens  |publisher=Blackie Academic & Professional |year=1996 |isbn=978-0-412-47350-0 |location=London |page=24 |access-date=25 November 2010}}</ref> This problem is compounded when food is then improperly [[Refrigeration|refrigerated]], allowing the endospores to germinate.<ref>{{cite journal | vauthors = McKillip JL | title = Prevalence and expression of enterotoxins in Bacillus cereus and other Bacillus spp., a literature review | journal = Antonie van Leeuwenhoek | volume = 77 | issue = 4 | pages = 393–399 | date = May 2000 | pmid = 10959569 | doi = 10.1023/A:1002706906154 | s2cid = 8362130 }}</ref> Cooked foods not meant for either immediate consumption or rapid cooling and refrigeration should be kept at temperatures below {{convert|10|C|F}} or above {{convert|50|C|F}}.<ref name="microorganisms.in.foods.p.242" /> Germination and growth generally occur between 10&nbsp;°C and 50&nbsp;°C,<ref name="microorganisms.in.foods.p.242" /> though some strains can [[Psychrotrophic bacteria|grow at low temperatures]],<ref>{{cite book | vauthors = Lawley R, Curtis L, Davis J |url=https://books.google.com/books?id=KiK9fcE4xvAC&pg=PA17 |title=The Food Safety Hazard Guidebook |publisher=[[Royal Society of Chemistry]] |year=2008 |isbn=978-0-85404-460-3 |location=Cambridge, UK |page=17 |access-date=25 November 2010}}</ref> and Bacillus cytotoxicus strains have been shown to grow at temperatures up to {{convert|52|C|F}}.<ref>{{cite journal | vauthors = Cairo J, Gherman I, Day A, Cook PE | title = Bacillus cytotoxicus-A potentially virulent food-associated microbe | journal = Journal of Applied Microbiology | volume = 132 | issue = 1 | pages = 31–40 | date = January 2022 | pmid = 34260791 | doi = 10.1111/jam.15214 | pmc = 9291862 | s2cid = 235906633 }}</ref> Bacterial growth results in production of [[enterotoxin]]s, one of which is highly resistant to heat and acids ([[pH]] levels between 2 and 11);<ref name="Todar22">{{cite web | vauthors = Todar K |title=''Bacillus cereus'' |url=http://textbookofbacteriology.net/B.cereus.html |access-date=19 September 2009 |work=Todar's Online Textbook of Bacteriology}}</ref> ingestion leads to two types of illness: diarrheal and emetic (vomiting) syndrome.<ref name="pmid155387092">{{cite journal | vauthors = Ehling-Schulz M, Fricker M, Scherer S | title = Bacillus cereus, the causative agent of an emetic type of food-borne illness | journal = Molecular Nutrition & Food Research | volume = 48 | issue = 7 | pages = 479–487 | date = December 2004 | pmid = 15538709 | doi = 10.1002/mnfr.200400055 }}</ref> The enterotoxins produced by ''B. cereus'' have beta-hemolytic activity.<ref name="Drobniewski-1993"/>
* The diarrheal type is associated with a wide range of foods, has an 8-to-16-hour [[Incubation period|incubation time]], and is associated with diarrhea and gastrointestinal pain. Also known as the 'long-incubation' form of ''B.&nbsp;cereus'' food poisoning, it might be difficult to differentiate from poisoning caused by ''[[Clostridium perfringens]]''.<ref name="Todar22"/> Enterotoxin can be inactivated after heating at {{convert|56|C|F}} for 5 minutes, but whether its presence in food causes the symptom is unclear, since it degrades in stomach enzymes; its subsequent production by surviving ''B.&nbsp;cereus'' spores within the [[small intestine]] may be the cause of illness.<ref name="watson19983">{{cite book | vauthors = Millar I, Gray D, Kay H |title=Natural Toxicants in Food |date=1998 |publisher=CRC Press |isbn=978-0-8493-9734-9 | veditors = Watson DH |pages=133–134 |chapter=Bacterial toxins found in foods |chapter-url=https://books.google.com/books?id=yKIy-iHLaiEC&pg=PA134}}</ref>
* The 'emetic' form commonly results from rice which is cooked at a time and temperature insufficient to kill any spores present, then improperly refrigerated. The remaining spores can produce a [[toxin]], [[cereulide]], which is not inactivated by later reheating. This form leads to nausea and vomiting 1–5 hours after consumption. Distinguishing from other short-term bacterial foodborne intoxications, such as by ''[[Staphylococcus aureus]],'' can be difficult.<ref name="Todar22"/> Emetic toxin can withstand {{convert|121|C|F}} for 90 minutes.<ref name="watson19983" /> As a result of the emetic type's association with rice, it is sometimes referred to colloquially as 'fried rice syndrome'.<ref>{{Cite web |last=Ross |first=Rachel |date=2019-05-01 |title=Bacillus Cereus: The Bacterium That Causes 'Fried Rice Sydrome' |url=https://www.livescience.com/65374-bacillus-cereus-fried-rice-syndrome.html |access-date=2023-08-19 |website=livescience.com |language=en}}</ref><ref>{{Cite web |last=Pelegrino |first=Elton N. |date=2021-09-10 |title=Fried Rice Syndrome: A common cause of food poisoning |url=https://www.nnc.gov.ph//regional-offices/mindanao/region-ix-zamboanga-peninsula/5946-fried-rice-syndrome-a-common-cause-of-food-poisoning |access-date=2023-08-19 |website=www.nnc.gov.ph |language=en-gb}}</ref><ref>{{Cite web |title=SFA {{!}} Fried Rice Syndrome |url=https://www.sfa.gov.sg/food-information/risk-at-a-glance/fried-rice-syndrome |access-date=2023-08-19 |website=www.sfa.gov.sg}}</ref>

The diarrhetic syndromes observed in patients are thought to stem from the three toxins: [[hemolysin]] BL (Hbl), nonhemolytic [[enterotoxin]] (Nhe), and [[cytotoxin]] K (CytK).<ref>{{cite journal | vauthors = Guinebretière MH, Broussolle V, Nguyen-The C | title = Enterotoxigenic profiles of food-poisoning and food-borne Bacillus cereus strains | journal = Journal of Clinical Microbiology | volume = 40 | issue = 8 | pages = 3053–3056 | date = August 2002 | pmid = 12149378 | pmc = 120679 | doi = 10.1128/JCM.40.8.3053-3056.2002 }}</ref> The ''nhe''/''hbl''/''cytK'' genes are located on the chromosome of the bacteria. Transcription of these genes is controlled by ''PlcR''. These genes occur in the taxonomically related [[Bacillus thuringiensis|''B.&nbsp;thuringiensis'']] and [[Bacillus anthracis|''B.&nbsp;anthracis'']], as well. These enterotoxins are all produced in the small intestine of the host, thus thwarting digestion by host endogenous enzymes. The Hbl and Nhe toxins are pore-forming toxins closely related to [[ClyA]] of ''[[Escherichia coli|E.&nbsp;coli]]''. The proteins exhibit a conformation known as a "[[beta-barrel]]" that can insert into cellular membranes due to a [[hydrophobic]] exterior, thus creating pores with [[hydrophilic]] interiors. The effect is loss of cellular [[membrane potential]] and eventually cell death.{{citation needed|date=December 2022}}

Previously, it was thought that the timing of the toxin production was responsible for the two different courses of disease, but it has since been found that the emetic syndrome is caused by the toxin [[cereulide]], which is found only in emetic strains and is not part of the "standard toolbox" of ''B.&nbsp;cereus''. Cereulide is a cyclic polypeptide containing three repeats of four amino acids: {{sc|D}}-oxy-{{abbr|[[Leucine|Leu]]|leucine}}—{{sc|D}}-{{abbr|[[Alanine|Ala]]|alanine}}—{{sc|L}}-oxy-{{abbr|[[Valine|Val]]|valine}}—{{sc|L}}-{{abbr|Val|valine}} (similar to [[valinomycin]] produced by ''[[Streptomyces griseus]]'') produced by [[Nonribosomal peptide|nonribosomal peptide synthesis]]. Cereulide is believed to bind to 5-hydroxytryptamine&nbsp;3 (5-HT3) [[serotonin]] receptors, activating them and leading to increased [[Afferent nerve fiber|afferent]] [[vagus nerve stimulation]].<ref>{{cite journal | vauthors = Agata N, Ohta M, Mori M, Isobe M | title = A novel dodecadepsipeptide, cereulide, is an emetic toxin of Bacillus cereus | journal = FEMS Microbiology Letters | volume = 129 | issue = 1 | pages = 17–20 | date = June 1995 | pmid = 7781985 | doi = 10.1016/0378-1097(95)00119-P }}</ref> It was shown independently by two research groups to be encoded on multiple [[plasmid]]s: pCERE01<ref>{{cite journal | vauthors = Hoton FM, Andrup L, Swiecicka I, Mahillon J | title = The cereulide genetic determinants of emetic Bacillus cereus are plasmid-borne | journal = Microbiology | volume = 151 | issue = Pt 7 | pages = 2121–2124 | date = July 2005 | pmid = 16000702 | doi = 10.1099/mic.0.28069-0 | doi-access = free }}</ref> or pBCE4810.<ref>{{cite journal | vauthors = Ehling-Schulz M, Fricker M, Grallert H, Rieck P, Wagner M, Scherer S | title = Cereulide synthetase gene cluster from emetic Bacillus cereus: structure and location on a mega virulence plasmid related to Bacillus anthracis toxin plasmid pXO1 | journal = BMC Microbiology | volume = 6 | pages = 20 | date = March 2006 | pmid = 16512902 | pmc = 1459170 | doi = 10.1186/1471-2180-6-20 | doi-access = free }}</ref> Plasmid pBCE4810 shares homology with the ''B.&nbsp;anthracis'' virulence plasmid pXO1, which encodes the [[anthrax toxin]]. Periodontal isolates of ''B.&nbsp;cereus'' also possess distinct pXO1-like plasmids. Like most of cyclic peptides containing nonproteogenic amino acids, cereulide is resistant to heat, proteolysis, and acid conditions.<ref>{{cite journal | vauthors = Stenfors Arnesen LP, Fagerlund A, Granum PE | title = From soil to gut: Bacillus cereus and its food poisoning toxins | journal = FEMS Microbiology Reviews | volume = 32 | issue = 4 | pages = 579–606 | date = July 2008 | pmid = 18422617 | doi = 10.1111/j.1574-6976.2008.00112.x | doi-access = free }}</ref>

''B.&nbsp;cereus'' is also known to cause difficult-to-eradicate chronic skin infections, though less aggressive than [[necrotizing fasciitis]]. ''B.&nbsp;cereus'' can also cause [[keratitis]].<ref name="pmid115810572">{{cite journal | vauthors = Pinna A, Sechi LA, Zanetti S, Usai D, Delogu G, Cappuccinelli P, Carta F | title = Bacillus cereus keratitis associated with contact lens wear | journal = Ophthalmology | volume = 108 | issue = 10 | pages = 1830–1834 | date = October 2001 | pmid = 11581057 | doi = 10.1016/S0161-6420(01)00723-0 }}</ref>

While often associated with gastrointestinal illness, ''B. cereus'' is also associated with illnesses such as fulminant bacterial infection, central nervous system involvement, respiratory tract infection, and endophthalmitis. Endophthalmitis is the most common form of extra-gastrointestinal pathogenesis, which is an infection of the eye that may cause permanent vision loss. Infections typically cause a corneal ring abscess, followed by other symptoms such as pain, proptosis, and retinal hemorrhage.<ref>{{Cite web | vauthors = McDowell RH, Sands EM, Friedman H |date=September 12, 2022 |title=Bacillus Cereus |pmid=29083665 |url=https://www.ncbi.nlm.nih.gov/books/NBK459121/ |access-date=October 27, 2022}}</ref> While different from ''B. anthracis, B. cereus'' contains some toxin genes originally found in ''B. anthracis'' that are attributed to anthrax-like respiratory tract infections.<ref name="Bottone-2010">{{cite journal | vauthors = Bottone EJ | title = Bacillus cereus, a volatile human pathogen | journal = Clinical Microbiology Reviews | volume = 23 | issue = 2 | pages = 382–398 | date = April 2010 | pmid = 20375358 | pmc = 2863360 | doi = 10.1128/CMR.00073-09 }}</ref>

A case study was published in 2019 of a [[catheter]]-related bloodstream infection of ''B.&nbsp;cereus'' in a 91-year-old male previously being treated with [[hemodialysis]] via PermCath for end-stage [[renal disease]]. He presented with chills, [[tachypnea]], and high-grade fever, his [[white blood cell count]] and [[high-sensitivity C-reactive protein]] (CRP) were significantly elevated, and [[CT imaging]] revealed a thoracic [[aortic aneurysm]]. He was successfully treated for the aneurysm with intravenous [[vancomycin]], oral [[fluoroquinolone]]s, and PermCath removal.<ref>{{cite journal | vauthors = Wu TC, Pai CC, Huang PW, Tung CB | title = Infected aneurysm of the thoracic aorta probably caused by Bacillus cereus: a case report | journal = BMC Infectious Diseases | volume = 19 | issue = 1 | pages = 959 | date = November 2019 | pmid = 31711418 | pmc = 6849281 | doi = 10.1186/s12879-019-4602-2 | doi-access = free }}</ref> Another case study of ''B. cereus'' infection was published in 2021 of a 30-year-old woman with lupus who was diagnosed with infective endocarditis after receiving a catheter. The blood samples were positive for B. cereus and the patient was subsequently treated with vancomycin. PCR was also used to verify toxins that the isolate produces.<ref>{{cite journal | vauthors = Ribeiro RL, Bastos MO, Blanz AM, Rocha JA, Velasco NA, Marre AT, Chamon RC, Rusak LA, Vivoni AM, Martins IS | display-authors = 6 | title = Subacute infective endocarditis caused by Bacillus cereus in a patient with Systemic Lupus Erythematosus | journal = Journal of Infection in Developing Countries | volume = 16 | issue = 4 | pages = 733–736 | date = April 2022 | pmid = 35544639 | doi = 10.3855/jidc.15685 | s2cid = 248717835 | doi-access = free }}</ref>

=== Diagnosis ===

In case of [[foodborne illness]], the diagnosis of ''B.&nbsp;cereus'' can be confirmed by the isolation of more than 100,000 ''B.&nbsp;cereus'' organisms per gram from epidemiologically implicated food, but such testing is often not done because the illness is relatively harmless and usually self-limiting.<ref name="cdc">{{cite journal|url=https://www.cdc.gov/mmwr/pdf/wk/mm4310.pdf |archive-url=https://ghostarchive.org/archive/20221009/https://www.cdc.gov/mmwr/pdf/wk/mm4310.pdf |archive-date=2022-10-09 |url-status=live|title=''Bacillus cereus'' food poisoning associated with fried rice at two child day care centers|journal=Morbidity and Mortality Weekly Report|publisher=[[Centers for Disease Control and Prevention]]|date=18 March 1994|volume=43|issue=10}}</ref>

=== Prognosis ===
Most emetic patients recover within 6 to 24 hours,<ref name="pmid155387092"/> but in some cases, the toxin can be fatal via [[fulminant hepatic failure]].<ref>{{cite journal | vauthors = Takabe F, Oya M | title = An autopsy case of food poisoning associated with Bacillus cereus | journal = Forensic Science | volume = 7 | issue = 2 | pages = 97–101 | date = March–April 1976 | pmid = 823082 | doi = 10.1016/0300-9432(76)90024-8 }}</ref><ref>{{cite journal | vauthors = Mahler H, Pasi A, Kramer JM, Schulte P, Scoging AC, Bär W, Krähenbühl S | title = Fulminant liver failure in association with the emetic toxin of Bacillus cereus | journal = The New England Journal of Medicine | volume = 336 | issue = 16 | pages = 1142–1148 | date = April 1997 | pmid = 9099658 | doi = 10.1056/NEJM199704173361604 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Dierick K, Van Coillie E, Swiecicka I, Meyfroidt G, Devlieger H, Meulemans A, Hoedemaekers G, Fourie L, Heyndrickx M, Mahillon J | display-authors = 6 | title = Fatal family outbreak of Bacillus cereus-associated food poisoning | journal = Journal of Clinical Microbiology | volume = 43 | issue = 8 | pages = 4277–4279 | date = August 2005 | pmid = 16082000 | pmc = 1233987 | doi = 10.1128/JCM.43.8.4277-4279.2005 }}</ref><ref>{{cite journal | vauthors = Shiota M, Saitou K, Mizumoto H, Matsusaka M, Agata N, Nakayama M, Kage M, Tatsumi S, Okamoto A, Yamaguchi S, Ohta M, Hata D | display-authors = 6 | title = Rapid detoxification of cereulide in Bacillus cereus food poisoning | journal = Pediatrics | volume = 125 | issue = 4 | pages = e951–e955 | date = April 2010 | pmid = 20194285 | doi = 10.1542/peds.2009-2319 | s2cid = 19744459 }}</ref><ref>{{cite journal | vauthors = Naranjo M, Denayer S, Botteldoorn N, Delbrassinne L, Veys J, Waegenaere J, Sirtaine N, Driesen RB, Sipido KR, Mahillon J, Dierick K | display-authors = 6 | title = Sudden death of a young adult associated with Bacillus cereus food poisoning | journal = Journal of Clinical Microbiology | volume = 49 | issue = 12 | pages = 4379–4381 | date = December 2011 | pmid = 22012017 | pmc = 3232990 | doi = 10.1128/JCM.05129-11 }}</ref> In 2014, 23 newborns in the UK receiving [[total parenteral nutrition]] contaminated with ''B.&nbsp;cereus'' developed [[sepsis]], with three of the infants later dying as a result of infection.<ref>{{cite web |date=4 June 2014 |title=Medical safety alert: Lipid Phase only of Parenteral Nutrition – potential contamination with ''Bacillus cereus'' |url=https://www.gov.uk/drug-device-alerts/drug-alert-lipid-phase-only-of-parenteral-nutrition-potential-contamination-with-bacillus-cereus |publisher=UK Medicines and Healthcare products Regulatory Agency}}</ref><ref>{{Cite news | vauthors = Cooper C |date=1 July 2014 |title=Third baby dies from contaminated 'Total Parenteral Nutrition' drip feed |work=[[The Independent]] |url=https://www.independent.co.uk/life-style/health-and-families/health-news/third-baby-dies-from-contaminated-total-parenteral-nutrition-drip-feed-9576663.html |url-status=live |archive-url=https://web.archive.org/web/20190418220544/https://www.independent.co.uk/life-style/health-and-families/health-news/third-baby-dies-from-contaminated-total-parenteral-nutrition-drip-feed-9576663.html |archive-date=18 April 2019}}</ref>

=== Prevention ===
While ''B.&nbsp;cereus'' vegetative cells are killed during normal cooking, spores are more resistant. Viable spores in food can become vegetative cells in the intestines and produce a range of diarrheal enterotoxins, so elimination of spores is desirable. In wet heat (poaching, simmering, boiling, braising, stewing, pot roasting, steaming), spores require more than 5 minutes at {{convert|121|C|F}} at the coldest spot to be destroyed. In dry heat (grilling, broiling, baking, roasting, searing, sautéing), {{convert|120|C|F}} for 1 hour kills all spores on the exposed surface.<ref name="bremer">{{cite journal | vauthors = Soni A, Oey I, Silcock P, Bremer P | title = Bacillus Spores in the Food Industry: A Review on Resistance and Response to Novel Inactivation Technologies | journal = Comprehensive Reviews in Food Science and Food Safety | volume = 15 | issue = 6 | pages = 1139–1148 | date = November 2016 | pmid = 33401831 | doi = 10.1111/1541-4337.12231 | doi-access = free }}</ref> This process of eliminating spores is very important, as spores of ''B. cereus'' are particularly resistant, even after pasteurization or exposure to gamma rays.<ref name="Whole-Genome Characterization of Ba"/>

''B.&nbsp;cereus'' and other members of ''Bacillus'' are not easily killed by alcohol; they have been known to colonize distilled liquors and alcohol-soaked swabs and pads in numbers sufficient to cause infection.<ref>{{cite web |date=25 March 2011 |title=Notes from the Field: Contamination of alcohol prep pads with ''Bacillus cereus'' group and ''Bacillus'' species — Colorado, 2010 | work = Morbidity and Mortality Weekly Report (MMWR) | location = Atlanta, Georgia |url= https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6011a5.htm |url-status=live |archive-url=https://web.archive.org/web/20180701030750/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6011a5.htm |archive-date=1 July 2018 |publisher=[[Centers for Disease Control and Prevention]]}}</ref><ref>{{cite journal | vauthors = Hsueh PR, Teng LJ, Yang PC, Pan HL, Ho SW, Luh KT | title = Nosocomial pseudoepidemic caused by Bacillus cereus traced to contaminated ethyl alcohol from a liquor factory | journal = Journal of Clinical Microbiology | volume = 37 | issue = 7 | pages = 2280–2284 | date = July 1999 | pmid = 10364598 | pmc = 85137 | doi = 10.1128/JCM.37.7.2280-2284.1999 }}</ref>

A study of an isolate of ''Bacillus cereus'' that was isolated from the stomach of a sheep was shown to be able to break down β-[[cypermethrin]] (β-CY) which has been known to be an antimicrobial agent. This strain, known as GW-01, can break down β-CY at a significant rate when the bacterial cells are in high concentrations relative to the antimicrobial agent. It has also been noted that the ability to break down β-CY is inducible. However, as the concentration of β-CY increases, the rate of β-CY degradation decreases. This suggests that the agent also functions as a toxin against the GW-01 strain. This is significant as it shows that in the right concentrations, β-CY can be used as an antimicrobial agent against ''Bacillus cereus''.<ref>{{Cite journal |last1=Zhao |first1=Jiayuan |last2=Jiang |first2=Yangdan |last3=Gong |first3=Lanmin |last4=Chen |first4=Xiaofeng |last5=Xie |first5=Qingling |last6=Jin |first6=Yan |last7=Du |first7=Juan |last8=Wang |first8=Shufang |last9=Liu |first9=Gang |date=2022-02-15 |title=Mechanism of β-cypermethrin metabolism by Bacillus cereus GW-01 |url=https://www.sciencedirect.com/science/article/pii/S138589472104537X |journal=Chemical Engineering Journal |language=en |volume=430 |pages=132961 |doi=10.1016/j.cej.2021.132961 |s2cid=239126417 |issn=1385-8947}}</ref>