Difference between revisions of "Group B Strep and Pregnancy"

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Next, Whidbey et al. investigated if the increased expression of hemolysin in the hyper-hemolytic GBS strain (ΔcovR) activates an inflammatory response<ref name=gg/>. Whidbey et al. isolated RNA from GBS-infected hAECs four hours after infection, and they used qRT-PCR to examine any changes in the expression of inflammatory genes<ref name=gg/><ref name=pp>[Lembo, Annalisa, et al. “Regulation of CovR Expression in Group B Streptococcus Impacts Blood-Brain Barrier Penetration.” Molecular Microbiology, vol. 77, no. 2, 2010, pp. 431–443., doi:10.1111/j.1365-2958.2010.07215.x.]</ref>. The results, depicted in Figure 4, suggest that infection with ΔcovR caused a significant increase in the transcription cytokines (e.g., IL-6 and IL-8) in hAECs<ref name=gg/>.
+
Next, Whidbey et al. investigated if the increased expression of hemolysin in the hyper-hemolytic GBS strain (ΔcovR) activates an inflammatory response<ref name=gg/>. Whidbey et al. isolated RNA from GBS-infected hAECs four hours after infection, and they used qRT-PCR to examine any changes in the expression of inflammatory genes<ref name=gg/><ref name=pp>[Lembo, Annalisa, et al. “Regulation of CovR Expression in Group B Streptococcus Impacts Blood-Brain Barrier Penetration.” Molecular Microbiology, vol. 77, no. 2, 2010, pp. 431–443., doi:10.1111/j.1365-2958.2010.07215.x.]</ref>. The results, depicted in Figure 4, suggest that infection with ΔcovR caused a significant increase in the transcription of cytokines (e.g., IL-6 and IL-8) in hAECs<ref name=gg/>.
  
 
==Section 3==
 
==Section 3==

Revision as of 04:59, 6 April 2021

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Introduction

This artistic recreation, based on scanning electron microscopy (SEM), depicts a three-dimensional (3D), computer-generated image, of a group of Gram-positive, Streptococcus agalactiae (group B Streptococcus) bacteria. Photo Credit: Alissa Eckert, who is a medical illustrator at the CDC.


By Shawn Ruiz


Group B Strep (GBS), also known as Streptococcus agalactiae, is a Gram-positive, beta-hemolytic, catalase-negative, facultative anaerobe that is a normal component of the gastrointestinal and genitourinary tracts[1]. In fact, GBS colonizes the gastrointestinal and genitourinary tracts of up to 50% of healthy adults[2]. Most healthy adults who are colonized by GBS will not experience any symptoms or GBS-related infections. While the bacteria is usually harmless in healthy adults, it is a major cause of meningitis, pneumonia, and and sepsis in neonates[3]. Moreover, GBS is the leading infectious cause of neonatal mortality and morbidity in the United States; between four and six percent of babies who develop GBS disease die[4][5]. GBS causes both early onset (<7 days old) and late onset (7-90 days old) infections in neonates[4]. The main risk factor for an early-onset GBS infection in a neonate is colonization of a birthing person's genital tract with Group B strep during labor[4]. About one in four pregnant individuals carry GBS in their body[5]. If the bacteria is present in a pregnant person, it can be directly transferred to their baby in a multitude of ways. For example, GBS can travel from the vagina into the amniotic fluid where the baby can ingest it. The baby can also come into contact with the bacteria as they make their way down the birth canal[3]. In the early 1990s, the early GBS infection rate was 1.7 cases per 1,000 births[3]. In an effort to decrease this infection rate, the American Congress of Obstetricians and Gynecologists and the American Academy of Pediatrics recommended screening pregnant individuals for GBS before they go into labor[3]. As a result, it is now common practice to screen pregnant individuals for GBS at some point between 35 and 37 weeks of pregnancy[5]. Pregnant people who test positive for GBS are treated with intravenous antibiotics during labor[5]. Penicillin and ampicillin are the recommended antibiotics for intrapartum GBS prophylaxis[6]. If a pregnant person tests positive for GBS and they are treated with antibiotics during labor, the risk of their neonate developing a serious, life-threatening GBS infection drops by 80% [3]. Early GBS infection rates in the United States have significantly dropped (0.25 cases per 1,000 births) since these preventative measures went into effect around 1995[3]. While intrapartum prophylaxis to prevent GBS transmission from the birthing individual to their neonate during labor and delivery has proven to be effective, this preventative measure does not target in utero infections that occur earlier in pregnancy, and little is known about the mechanisms that result in the infection of the amniotic cavity[7]. In utero GBS infections have devastating effects, including preterm birth and mortality in both the pregnant person and their baby[7]. That said, the it is critical that researchers and public health officials work toward understanding exactly how GBS infects the amniotic cavity.

Section 1

GBS has been isolated from the amniotic fluid of birthing people with intact chorioamniotic membranes, suggesting that GBS is capable of invading and breaching amniotic epithelium and chorioamnion[7][8][9][10][11]. This led Whidbey et al. to hypothesize that “intra-amniotic GBS infections in patients with intact placenta or chorioamniotic membranes may be due to elevated virulence factor expression”[7][8][9][10][11].Previous studies showed that the expression of GBS virulence genes is regulated by a two-component regulatory system: COVR/S[7][12][13][14]. More specifically, COVR/S was described to repress a multitude of GBS virulence genes, including the cyl operon, which contains the cylE gene that is that is important for the production of the pluripotent toxin, hemolysin [7][12][13][14]. In order to test whether or not increased expression of GBS virulence genes promotes the invasion of amniotic epithelium, Whidbey et al. compared the abilities of wild-type (WT) GBS and hyper-hemolytic GBS (ΔcovR) GBS to adhere to and invade human amniotic epithelial cells (hAEC)[7].The hAECs were isolated and cultured from “normal, term placentas obtained immediately after cesarean delivery from” birthing people without labor[7]. Non-hemolytic GBS strains (ΔcovRΔcylE and ΔcylE) were also included in the experiment to investigate hemolysin’s role in GBS strains’ ability to adhere to and invade hAECs[7][15]. The results suggest that all GBS strains adhered to hAECs, as seen in Figure 2.

Figure 2. Primary hAECs were isolated from chorioamniotic membranes and the percent adherence of GBS WT, isogenic ΔcovR, ΔcovRΔcylE, and ΔcylE mutants were compared[7].[1].

Notably, as shown in Figure 3, WT GBS invaded hAECs (~4% invasion), non-hemolytic GBS showed a significantly decreased invasion when compared to the WT (~0.3% invasion), and the hyper-hemolytic strain (ΔcovR) was significantly more invasive when compared to the WT (~80% invasion)[7].

Figure 3. Primary hAECs were isolated from chorioamniotic the percent invasion of GBS WT, isogenic ΔcovR, ΔcovRΔcylE, and ΔcylE mutants were compared[7]. [2].

In sum, Whidbey et al. concluded that hemolysin promotes GBS invasion of hAECs.


Next, Whidbey et al. investigated if the increased expression of hemolysin in the hyper-hemolytic GBS strain (ΔcovR) activates an inflammatory response[7]. Whidbey et al. isolated RNA from GBS-infected hAECs four hours after infection, and they used qRT-PCR to examine any changes in the expression of inflammatory genes[7][16]. The results, depicted in Figure 4, suggest that infection with ΔcovR caused a significant increase in the transcription of cytokines (e.g., IL-6 and IL-8) in hAECs[7].

Section 3

Include some current research, with at least one figure showing data.

Section 4

Conclusion

References



Authored for BIOL 238 Microbiology, taught by Joan Slonczewski, 2021, Kenyon College.

  1. [“Streptococcus Agalactiae.” Wikipedia, Wikimedia Foundation, 24 Mar. 2021, en.wikipedia.org/wiki/Streptococcus_agalactiae.].
  2. [Johri, Atul Kumar, et al. “Group B Streptococcus: Global Incidence and Vaccine Development.” Nature Reviews Microbiology, vol. 4, no. 12, 2006, pp. 932–942., doi:10.1038/nrmicro1552.].
  3. 3.0 3.1 3.2 3.3 3.4 3.5 [Dekker, Rebecca. “The Evidence on: Group B Strep.” Evidence Based Birth , Evidence Based Birth , 17 July 2017, evidencebasedbirth.com/groupbstrep/.].
  4. 4.0 4.1 4.2 [Morgan, John A. “Group B Streptococcus And Pregnancy.” StatPearls [Internet]., U.S. National Library of Medicine, 29 Jan. 2021, www.ncbi.nlm.nih.gov/books/NBK482443/#:~:text=Preterm%20infants%20with%20early%2Donset,in%20term%20infants%5B2%5D.]
  5. 5.0 5.1 5.2 5.3 [“Group B Strep: Fast Facts and Statistics.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 11 June 2020, www.cdc.gov/groupbstrep/about/fast-facts.html#references.]
  6. [Horsley, Elizabeth. “CDC Updates Guidelines for the Prevention of Perinatal GBS Disease.” American Family Physician, The American Academy of Family Physicians Foundation , 1 May 2011, www.aafp.org/afp/2011/0501/p1106.html#:~:text=The%20recommended%20antibiotic%20for%20intrapartum,units%20intravenously%20every%20four%20hours.]
  7. 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 [Whidbey, Christopher, et al. “A Hemolytic Pigment of Group B Streptococcus Allows Bacterial Penetration of Human Placenta.” Journal of Experimental Medicine, vol. 210, no. 6, 2013, pp. 1265–1281., doi:10.1084/jem.20122753.]
  8. 8.0 8.1 [JR, Bobitt, and Ledger WJ. “Unrecognized Amnionitis and Prematurity: a Preliminary Report.” The Journal of Reproductive Medicine., vol. 19, no. 1, 30 June 1977, pp. 8–12., europepmc.org/article/med/874942.]
  9. 9.0 9.1 [Naeye , RL, and EC Peters. “Amniotic Fluid Infections with Intact Membranes Leading to Perinatal Death: a Prospective Study.” Pediatrics, U.S. National Library of Medicine, Feb. 1978, pubmed.ncbi.nlm.nih.gov/634667/.]
  10. 10.0 10.1 [Winram, Scott B., et al. “Characterization of Group B Streptococcal Invasion of Human Chorion and Amnion Epithelial Cells In Vitro.” Infection and Immunity, vol. 66, no. 10, 1998, pp. 4932–4941., doi:10.1128/iai.66.10.4932-4941.1998.]
  11. 11.0 11.1 [Goldenberg, Robert L., et al. “Intrauterine Infection and Preterm Delivery.” New England Journal of Medicine, vol. 342, no. 20, 2000, pp. 1500–1507., doi:10.1056/nejm200005183422007.]
  12. 12.0 12.1 [Lamy, Marie-Cécile, et al. “CovS/CovR of Group B Streptococcus: a Two-Component Global Regulatory System Involved in Virulence.” Molecular Microbiology, vol. 54, no. 5, 2004, pp. 1250–1268., doi:10.1111/j.1365-2958.2004.04365.x.]
  13. 13.0 13.1 [Jiang, Sheng-Mei, et al. “Variation in the Group B Streptococcus CsrRS Regulon and Effects on Pathogenicity.” Journal of Bacteriology, vol. 190, no. 6, 2008, pp. 1956–1965., doi:10.1128/jb.01677-07.]
  14. 14.0 14.1 [Rajagopal, Lakshmi, et al. “Regulation of Cytotoxin Expression by Converging Eukaryotic-Type and Two-Component Signalling Mechanisms in Streptococcus Agalactiae.” Molecular Microbiology, vol. 62, no. 4, 2006, pp. 941–957., doi:10.1111/j.1365-2958.2006.05431.x.]
  15. [Pritzlaff, Craig A., et al. “Genetic Basis for the Beta-Haemolytic/Cytolytic Activity of Group B Streptococcus.” Molecular Microbiology, vol. 39, no. 2, 2001, pp. 236–248., doi:10.1046/j.1365-2958.2001.02211.x.]
  16. [Lembo, Annalisa, et al. “Regulation of CovR Expression in Group B Streptococcus Impacts Blood-Brain Barrier Penetration.” Molecular Microbiology, vol. 77, no. 2, 2010, pp. 431–443., doi:10.1111/j.1365-2958.2010.07215.x.]