July 26 Flu

not sure how much I'll get with just one hand but I'll give it a go:

x ray of my hand, you can see the dislocation of the ulna upward from the normal position

Review:
group work: 5 top ways (activities) to get HIV

Why HIV/AIDS is unusual:

Why no vaccine: 
            -HIV evolves rapidly (many strains and types) 
            -Ethical testing of vaccine?

Transmission depends upon many factors:
          - viral load of the body fluids varies
         - body fluid has cells? 
        - case of entry of virus into bloodstream 
                * trauma (rape, or anal) 
                * presence of other sexually transmitted diseases

Transmission of HIV
********(Ranked in order of likelihood of infection) group work question********

1. blood or blood products introduced IV
      * blood transfusion with contaminated blood (untested)
      * contaminated clotting factor
      * IV drug users: needle sharing
 1b miscellaneous blood or body fluid exchange
2. perinatal (placental or during birth)
3. rape/ anal intercourse as receiving partner
4. vaginal intercourse as receiving partner
5. sexual intercourse as donating partner or oral sex

Topic 8b: Influenza

*old flu, bird flu, swine flu
pic: kid kiss pig

Influenza viruses

Type A: world wide pandemics, infect all mammals and birds

Type B:small epidemics in vulnerable populations, infect mammals only

Type C:infect mammals only, rarely causes disease in humans

Structure of Type A  (Box. p. 736)

Genome: RNA virus : 8 strands/ inside capsids

Enveloped

with matrix protiens: ion channel M2

Two important peplomer types:

Hemagglutinin

Function:host cell binding

Blocked by drugs: amantidine/ rimantidine (blocks uncoating)

Neuraminidase

Function: helps release progeny

Blocked by drugs: Tamiflu & Relenza (only these 2 drugs work on swine flu and bird flu)

Why do you need a new shot every year?

The viruses change!

*body recognizes virus by anatomical parts (antigen)

HA –hemagglutinin antigen

NA –neuraminidase antigen

We identify flu viral types by:

* numbering antigens
*location/date first isolated in humans

sleeve from flu shot: split virion inactive ultra violet, centrifug.....

Flu “shot” is: soluble subunit

Flu-mist vaccine is: live attenuated virus

list if year by year flu shot

3 Viral types seen in annual seasonal vaccines are:   
             *Two type A (H1N1 and H3N2) and one type B

*high rate of genetic (thus antigenic) change within & between flu seasons
*vaccine is a cocktail of international influenza committee's best guess for this year's strains
           

Two means of genetic change in flu viruses:  Fig. 25.38

Antigenic Drift

* tiny mutations introduce small antigenic changes (RNA virus more mutations)
* gradual changes in viruses over time

fig 25.38

Antigenic Shift

(reassortment)
*2 flu viruses infect same host cell
*New viral hemagglutinin (or less commonly, neuraminidase) in existing viruses

*****break*****

Connections between human / pig / bird flu viruses:

* humans and pigs can share viruses
* pigs and birds can share viruses
* humans normally can't get it directly from birds

*pigs are mixing pot where human, pig, and bird virus can co-infect same cell

*****draw this?***draw human cell and human flu and able to match receptor proteins and infect cell....pigs and humans both have human and pig flu receptors..wild card birds....share with pigs not human*****

* non human flu viruses are very different from human viruses(all 8 RNA strands and all

Why is the new H5N1 bird flu virus of concern?

highly lethal/ virulent: rare human cases of bird flu are often lethal
* (but so far. poorly passed from person to person): mutation needed to be pandemic

Why is the new H1N1 swine flu virus of concern?

* is moderately virulent in US

       * return highly virulent like 1918-1919 "Spanish flu"
* Easily passed from person to person

Where do flu viruses live between epidemics?

* probably reservior animals
* migratory or domestic birds

*****group activity*****
*does this image antigenic drift or shift? define both . why

Last Lab day pictures

pictures from last day of lab. only test now....break over... label these later....


Row 1 Water from creek off of Florida St. 


 

 

Row 6 water analysis

 Our unknown Coagulase test: NEGATIVE

 our unknown tubes (which we tossed today)

Unknown 5 A MSA plate: Staph. epidermis

July 25th HIV/AIDS lecture continued

*** review.***

The rise of AIDS:

#1 cause of death in Africa, #4 worldwide in the US - charting the causes of death in the 25-44 age range: Men (top) note: since 1994 AIDS is the leading cause of death
Women

********

–What caused the virus to spread beyond small, contained outbreaks to become epidemic and then pandemic?

 roads and planes and more travel and movement.

Structure of HIV-1 (Box p. 726)

Genome: ______2____ identical (duplicate) strands of ___RNA_________.

Enzymes:

1-Reverse transcriptase

2- Integrase

3- protease

3 surrounding layers:

Capsid

Layer of ____matrix (tegument)_______________ proteins

Envelope (plasma membrane taken from ______peplomers_________________)

http://www.youtube.com/watch?v=9leO28ydyfU

*** see video posted on blackboard***

2 proteins make up peplomers:

–Head = gp 120

–Stalk = gp 41

HIV-1 Life Cycle (Fig. 25.19)

1- ATTACHMENT  (Fig. 25.20)

Viral - gp-120 attaches to host cells CD-4 receptor site and co-receptor.

CD-4 cell types:
1. -T helper,
2.- Macrophages:includes fixed cells such as  Dendrite Kuppfer, microglial cells;
3.smooth muscles

***

2. Penetration
* Fusion of host cell and viral envelope (gp-41); * Uncoating
* Fusion inhibitor drugs: block penetration of virus (gp-41 interference)
*** list of drugs: Fuzeon, Selzentry ...

******stop and draw two steps on big chart************



 
*** she labels the drug targets: fusion and penetration inhibitors**** she drew step 1 and 2****

3. Reverse Transcription step

target drug::::: AZT (*** remember this one, oldest drug, approved for pregnant mothers) , dd1, ddC, d4T, 3TC (7 drugs + 7 combinations)

 Nucleoside reverse transcription inhibitors (chapter 10)

 * Base analogue- drugs replace nucleotides in DNA (roadblock)
             -AZT, dd1, ddC, d4T, 3TC (7 drugs + 7 combinations)

 * mistake because viral enzyme are fast and sloppy

Fig. 10.7 common nucleoside (base analogue) antiviral drugs




Non-nucleoside reverse transcriptase inhibitors
      * affect reverse transcriptase enzyme directly
      * 4 drugs, 1 combination


4. Incorporation
  * Integration of viral DNA into genome using integrase
  * Integrase inhibitor drugs block incorporation


 
*** my youtube channel for Microbiology: Microbiology Youtube channel

I'll add more videos when I get a chance.

*** stop and draw two steps on diagram.....draw host DNA, Reverse transcriptase enzyme makes viral DNA from viral RNA....viral DNA becomes double stranded and attach to host DNA.. becomes provirus... step 3: reverse transcription label... step 4. incorporation label...put drug targets on for those two steps: protein inhibitors * nucleoside RT inhibitors * non-nucleoside RT inhibitors *D0 integrase inhibitors*****break*****

5. Synthesis (no drug targets)
 transcription of incorporated viral DNA into viral RNA
Newly made strands produced are used to :
1. genome copies for new viruses
2. mRNA to be translated into proteins

Protiens MADE:

Gp-120 and gp-41 proteins (peplomers parts) are produced in cytoplasm and immediately go to cell membrane
protease and integrase enzymes
other proteins made in large multi-proteins to be cut into small proteins with protease later
    - Final enzyme reverse transcriptase
   -capsid building blocks = capsomers
   - stabilizing proteins = matrix proteins

6.  Assembly
   * components move to cell surface
    * (completed after release)

7. Release by budding
-Envelope and peplomers wrapped around proteins and genome

6B Maturation (finish assembly) (9 drugs + 1 combination)

* Protease Inhibitors block:
      - cutting multi-protein into individual:
                - capsomeres
                - matrix proteins
               - enzymes






*** add to picture.... regular transcription.. viral RNA is going to be conserved and used as genome copies... some are to be translated by ribosome into viral proteins.....you will make peplomer proteins separately (gp140 and gp41)integrase separately, protease separately, the rest made in a long protein containing: capsomers, matrix proteins, reverse transcriptase enzyme......synthesis starts where you make the RNA and when you make the proteins.......NO new drugs to add to synthesis step... now move on to Assembly... peplomer proteins go into the membrane.. genome , protease, integrase, multiprotein gather down near section where peplomer proteins go.....this is stage 6, assembly, nothing unusual.. no drug targets.....7. release through budding....cell surface will have surface molecules, peplomer proteins, genome copies inside, protease, integrase inside, and then the multiprotein which has reverse transcriptase, capsomers and matris.....this is step 7.. no drug targets for budding but where you will see the final drug target is when protease cut the multiprotein into various places and folding occurs and the entire virus is done.. matrix right under envelope to stabilize it... then capsid inside of that and then genome and protease and integrase and reverse transcriptase.....drug target E: protease inhibitor***

Sample test question: 1. which viral enzyme is used first after it is made? protease
2. which viral enzyme is used first in the new host cell? reverse transcriptase

------------------------------------------------------------------------------------------------------------------------------------------------

Progression of HIV Disease    Fig. 25.21

Stage one: occurs ___weeks_____ after infection

Symptoms are : flu-like, swollen lymph nodes.

What is happening to CD-4 cells are killed after 6 hours but replaced by stem cells from your bone marrow

Immunocompentence is still high.

Stage two:  occurs _months___ after infection

 - no symptoms

 - CD-4 cells replaced (may have swollen lymph nodes but some people have it normally)

Stage three:  occurs __years___ after infection

Symptoms are: immune response failing (CD-4 replacement decreased)

********(babies infected by mom, will be at this stage by the time they are 2 years old)

 - opportunistic infections begin: (most common)
      * Pneumocystis carmi pneumonia (eukaryotic parasite, does not respond to antibodies or antiviral)
      * repeated severe, or systemic yeast infections
      * Cryptosporidium diarrhea ( a liter of fluid an hour, cloridine resistant)
      * Herpes inflections (simplex, zoster (shingles), CMV (causes blindness))

**** Table 25.5 ***

Stage four: (also called __AIDS__) occurs __years (often 15 or more)____ after infection

What is happening to CD-4 cells: drops below 200 cells/microliter

Symptoms include: opportunistic disease and other unusual diseases appear:
    * Prior opportunists: more common and sever
    * M. tuberculosis/ M. aviium complex (MAC) (acid fast)

    * cancers (Kaposi's sarcoma) Fig. 18.25
    * wasting disease (your body digest your own tissues)

Why HIV/AIDS is unusual:

Why no vaccine: 
            -HIV evolves rapidly (many strains and types) 
            -Ethical testing of vaccine?

Transmission depends upon many factors:
          - viral load of the body fluids varies
         - body fluid has cells? 
        - case of entry of virus into bloodstream 
                * trauma (rape, or anal) 
                * presence of other sexually transmitted diseases

Transmission of HIV
(Ranked in order of likelihood of infection)

July 24: degranulation, vaccines, HIV/AIDS

review:
* Effects from release of granule chmicals may be local (poison ivy, "hay fever) or systemic (anaphylactic reaction to bee sting)

* General inflammation

* smooth muscle contraction:
          - constriction of respiratory pathways (shortness of breath)
          - cramping of GI tract (often also diarrhea)

* capillaries dilate and become leaky (fluid into tissues)
          - swelling, hives, burning and itching

 

 * glandular secretion
     - Mucus = runny nose
     - Tears = watery eyes

* why?
     - Expel antigen bearing structures from body
     - worm and protozoa antigens are similar to allergens
           -immune system mistake? 

***(hygiene hypothesis: exposure to parasites early in life will use this response to get rid of worms and protozoa, but if you body never get expose to them then your body will react to allergens because they are similar to the antigens of worms and protozoa) ****

  Table 18.1

Use of Immunology – Vaccine Production      Table 17.2

Why are vaccines given if not 100% safe?

Example:  Measles, Mumps, Rubella

Risks associated with disease:
     -Measles 

• death 1 in 3000
• pneumonia 1 in 20
• encephalitis 1 in 2000 (deafness, blindness, mental retardness, etc)

* Mumps: encephalitis 1 in 300

* Rubella: congential rubella syndrome 1 in 4 (birth defects)

Risks associated with vaccine:

                   * Encephalitis or allergic reaction: 1 in 1, 000, 000

Mercury compound removed 20 years ago: no autism change in results... autism is diagnosed about the same time they are getting vaccine but no direct link, but could be linked....

Vaccine Production    (PRINT OUT and complete Vaccine Type Comparison Chart)

* Provide exposure to antigen without disease 

     * Whole cell vaccines: Entire cell, with multiple antigens present to give strong reaction
              * Attenuated = live (weakened but not dead; Pasteur)
                      - Multiple antigens = multiple types of memory cells

                      - reproduce in body to amplify response - highest # of memory cells

                      - slight danger of infection/ reaction 

                            (example: Koch's failed tubercolis vaccine, live Polio virus, post Polio syndrome....)

 

Vaccine type	Effectiveness (high  to  low) & why	Risk (high to low) & why
Whole cell attenuated	high effectiveness, multiple antigens and copies	low risk of infection,  risk of negative reaction
Whole cell killed	high effectiveness, multiple antigens, no copies	no risk of infection,  risk of negative reaction
Soluble Subunit	low, individual antigens	no risk of infection, less risk of allergic reaction *unless you are allergic to adjuvant*
Recombinant whole cell attenuated
Recombinant whole cell non-pathogen
Recombinant soluble subunit

Whole cell vaccines:  ___live whole cell of pathogen____injected into your body

Attenuated = ___live but weakened___

Effectiveness and why:
* multiple antigens = multiple types of memory cells
* reproduce in body to amplify response = highest # of memory cells

Risk level: Slight danger of infection/ reaction

Killed or inactivated vaccines:

Effectiveness and why:
* No reproduction, but still multiple antigens
* No danger of infection, but reaction possible

Risk level:no risk of infection,  risk of negative reaction

******diagram of whole cell vaccines....flu shot = peplomers not the whole cell.****

Soluble antigens (subunits): __subunits____ injected into your body

Effectiveness and why:
* less effective because only response to only single antigen injected
* response to soluble antigens may be lower than cell bound antigens

Adjuvants

Risk level: no danger of infection, lower chance of reaction

****** newest vaccines are manipulation of genes********

Recombinant vaccines:  

created by_removing genes for production of pathogen's antigens_____   Fig. 17.2

Attenuated (pathogen): safer

Effectiveness and why: cut out genes that makes it virulent,

(example capsule gene cut out...gene c.. enzyme... toxin.. whatever dangerous component was, you will get fewer memory types because you took out some genes that made some antigens but they will reproduce and make copies) assured to be safer, relative high effectiveness with higher safety

Risk level: much lower then live unattenuated pathogen

Whole cell (non pathogen): harmless cell reproduces in body with antigens

Effectiveness and why: you take a nonpathogenic cell (like yeast) and give it a gene (like gene a or b that is non pathogenic) to the nonpathogenic cell. the cell will produce the antigen, the cells will reproduce... you will not get a lot of memory cell types but you will get a lot of memory cells for that antigen...

Risk level: no risk of infection, low risk of allergic reaction

Soluble subunit: harmless cell secretes soluble antigens

Effectiveness and why: less effective give you one memory cell type, no reproduction so no copy of memory cell type, cheaper and safer then real pathogen vaccine

Risk level: low

Newest (coming soon?) vaccine type: DNA vaccine? the antigens will be expressed by your own cells? insert plasmid with antigen-producing gene into your own cell- produces antigen inside the body.

Common vaccines used today:  Table 17.2

* group activity: List the stages of the HIV life cycle
   - note: it's a retrovirus, so it has 7 stages
   - it is an unusual virus, so one of the stages isn't finished until after it leaves the host cell, which is that?

1. attachment 2. penetration 3. reverse transcription 4. incorporation 5. synthesis 6. assembly 7. budding/ release

*which is not finished until after budding? assembly/ maturation step? it is when protease makes capsomere

drug targets.... expand upon it... draw the life cycle but right now we will talk about the history...

Topic 8a: HIV Disease and AIDS

(Acquired Immune Deficiency Syndrome)

Global Impact of HIV / AIDS:

* people living with HIV.... 33.4 million
* New HIV infection in 2008... 2.7 million
* Deaths due to AIDS in 2008... 2.0 million

parts of the world most impacted by the HIV/AIDS pandemic: subSahara Africa (1.9 million)

2nd: South and Southeast Asia (different strain and much more aggressive)

Deaths due to AIDS, 2011 chart..


 

 

Origin of HIV-1

* Most similar virus: SIV (simian immunodeficiency virus) in primates

Probably entered humans from similar___SIV (simian immunodeficiency virus)___

in __Sub-saharan Africa___(geographical area) around __1959___ (year)

–What activity probably led to species-jumping?

* contact between infected primates (primary food source) and humans allowed species jumping

Final Extra Credit article

Pseudomonas Biofilms, Cystic Fibrosis, and Phage: a Silver Lining?

1. Harald Brüssow

+ Author Affiliations

1. Nestlé Research Center, BioAnalytical Department, Food and Health Microbiology Group, Lausanne, Switzerland

1. Address correspondence to harald.bruessow@rdls.nestle.com.

 

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ABSTRACT

In contrast to usual laboratory conditions, most bacteria in the human body grow in biofilms. Encased in a structured matrix, many pathogens display heightened resistance to antibiotics. Pseudomonas aeruginosa lung infections in cystic fibrosis patients represent a prime example of the clinical challenges that antibiotic resistance in biofilms can represent. In the March 6, 2012 issue of mBio, Colin Hill and his colleagues report on experiments that add to the evidence that Pseudomonas phages are a potential treatment option for these infections.

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Commentary

With an incidence of 1 out of 3,500 live births, cystic fibrosis (CF) is the most common life-threatening autosomal recessive genetic disease in Caucasian children. The causative mutations are located within a single gene, the CF transmembrane regulator. Half of the affected patients show a deletion of a specific phenylalanine residue (ΔF508), but the genotype-phenotype relationship is complex. It has been proposed that the strikingly high prevalence of this deleterious mutation could be due to a higher resistance to toxin-induced diarrhea or tuberculosis among heterozygotes.

CF affects the gut and the pancreas (exocrine pancreas insufficiency leads to malabsorption and failure to thrive), but for most CF patients, life expectancy is determined by the development of lung disease. The failure to clear thick and abundant mucous secretions from the lung leads to chronic coughing at a young age, followed by frequent lung infections, including repetitive episodes of pneumonia. Chest percussion to remove the secretions and antibiotics constitute a mainstay of treatment. However, for most CF patients, recurring lung infections finally lead to end-stage lung disease, which can be treated only with lung transplantation. The median survival age for CF patients is currently >32 and 29 years for men and women, respectively.

The microbiology of CF is complex. Staphylococcus aureus colonizes the lung in 30% of CF patients early in life. Small, slow-growing colony variants displaying antibiotic resistance, including methicillin-resistant S. aureus (MRSA) strains, are characteristically found. In early adolescence, the lungs typically become chronically infected with Pseudomonas aeruginosa; up to 80% of adult CF patients are colonized with this pathogen. Nonmotile, anaerobic, mucoid variants of P. aeruginosa grow in a biofilm within the lungs, a structure that confers resistance to antimicrobials.

Since today’s CF patients reach adulthood, still other facultative pathogens have a chance to enter the lung. Bacteria of the Burkholderia cepacia complex, for instance, are now recovered from 10% of the lungs in adult CF patients. Burkholderia infections can transform a mild pulmonary case into a rapidly deteriorating lung infection associated with bacteremia and death within 6 months. Even among patients with a less dramatic course, some surgeons consider Burkholderia infections to be a contraindication for lung transplantation. In hospital settings, Burkholderia-infected patients should be segregated from other CF patients to prevent nosocomial spread of the pathogen.

Since lung infections are the life-limiting factor for CF patients and since the major CF pathogens are increasingly difficult to treat with antibiotics, alternatives or adjuncts to antibiotics are urgently needed. The mBio article by Colin Hill and his colleagues (1) provides an encouraging outlook in this regard. The authors explored the possibility of treating P. aeruginosa infections with bacteriophages, an attractive potential therapeutic option for several reasons.

First, S. aureus and P. aeruginosa are classical targets of the Soviet phage therapy approach. The Russian company Microgen currently sells phage preparations against both pathogens, either singly or in combination, for treatment of pyogenic infections. Frequently used for treating pulmonary infections, these products are registered medicines in Russia. Second, it is relatively easy to isolate “virulent” (as opposed to “temperate”) phages against the three major pathogens of CF patients. Large collections of phages of S. aureus, P. aeruginosa, and B. cepacia exist, many of which are fully sequenced. This is not a trivial statement, since phages are not isolated easily against any bacterial species.

Third, the aforementioned phages have a broad host range. Unlike antibiotics, most phages are strain specific, making them targeted to the pathogen of interest and preventing collateral damage to commensal bacteria. However, this specificity can be a problem for treatment, and often a cocktail of different phages is needed to achieve a reasonable coverage of a given pathogenic species. Fortunately, phages against CF pathogens have a good, if not an excellent, pathogen coverage. Phage K, for instance, infects nearly half of S. aureus isolates from large collections, and phage Stau2 infects 80% (2).

Fourth, the efficacy of phage therapy approaches has been demonstrated in animal infection models with CF pathogens. For example, B. cenocepacia bacterial density in the lung was reduced after intraperitoneal but not intranasal phage application to mice. The lytic effect was specific to the replication-competent phages, since no lytic effect was seen with UV-inactivated phages or a phage that had no in vitro lytic activity against the infecting Burkholderia strain. Phages showed amplification in the lung and reduced pathogen-induced inflammation signs. In treated mice, phages were colocalized with degraded bacteria in perivascular lung areas and alveolar septa (3).

The recent article by Alemayehu et al. (1) provides suggestive evidence that bacteriophages might also be of use against P. aeruginosa infection. They showed that suitable phages can be isolated from sewage, a common starting material for phage isolation. By sequencing the phage, they demonstrated the absence of undesired genes in their therapeutic phages, an essential condition for later phage application in human subjects. They then reported that the phages infect Pseudomonas growing in a biofilm. Finally, the authors demonstrated the efficacy of intranasally applied phages in a P. aeruginosa lung infection model using state-of-the-art imaging techniques (although it should be noted that mice do not get chronically infected with P. aeruginosa, so biofilms are thus not formed in this transient infection model). Mice treated with intranasal phage at a phage-to-bacterium ratio of 1:1, but not with lower ratios, survived a lethal P. aeruginosa infection.

The data reported by Alemayehu et al. (1) confirm previous observations from other groups and therefore represent important steps toward developing effective CF phage therapy.

Fittingly, work on phage therapy for P. aeruginosa infection continues at the Pasteur Institute in Paris, where phages and phage therapy were first described by Felix d’Herelle nearly 100 years ago. Using bioluminescent P. aeruginosa, Debarbieux et al. (4) demonstrated a rapid killing of bacteria in phage-treated animals and a reduction in inflammatory markers. The researchers selected phages which grew well on clinical P. aeruginosa isolates from CF patients and showed that they achieved dose-dependent protection in a mouse lung infection model (5). Phages showed in vivo replication, decreased the alveolar pathogen load, and prevented histopathologic lesions. Phage treatment could be delayed for a few hours with the same results, and administering the phages a day before pathogen challenge also prevented the infection. When phages were administered to uninfected mice, they persisted for 5 days in the lung, suggesting the potential for preventive phage use.

Similarly, the biofilm activity of Pseudomonas phages reported in the Alemayehu et al. article confirms earlier work. British researchers found that phages had bacteriocidal effects on Pseudomonas in biofilms (6). When using excess phages, a 100-fold bacterial titer decrease was observed. Pseudomonas phages could also diffuse through 8% alginate gels, which mimic the conditions in Pseudomonas biofilms. Digestion fragments from the alginate were released from phage-treated polymers. Phage researchers from the Republic of Georgia and structural biologists subsequently showed that the depolymerizing enzyme is part of the phage particles (7, 8).

Pretreatment with phages may also eventually be feasible. Researchers at the Centers for Disease Control and Prevention (CDC) in Atlanta, GA, demonstrated that pretreating catheters with a cocktail of Pseudomonas phages prevented biofilm formation. Intact but not heat-killed phages achieved a 1,000-fold titer reduction of the bacteria in the biofilm grown on a catheter in the presence of human serum (9). The latter observation is important, since in the transition from bench to bed, the devil is in the details. The lead authors of the Alemayehu article observed this for themselves in earlier work, in which they explored the potential of S. aureus phages for treating bovine mastitis. In that study, they found that milk contained an inhibitory activity that inactivated the broad-host-range S. aureus phage K (10), a fact that explains the observations from Canadian researchers who failed to detect an in vivo inhibitory effect of phages on bovine mastitis.

Despite the setbacks with S. aureus phage use in farm animals, the prospects for applying Pseudomonas phages in humans are encouraging. Three clinical trials that address Pseudomonas infections in venous leg ulcers (Intralytix), burn patients (Belgian military) (11), and the outer ear canal (causing diseases ranging from mild swimmer’s ear to necrotizing otitis externa in diabetics and AIDS) (Biocontrol, United Kingdom) have been registered. So far, no adverse effects of phage treatment have been observed. In a controlled phase II clinical trial, 24 otitis externa patients received either a single small dose of Pseudomonas phage cocktail or a placebo. The researchers found evidence for in vivo phage replication, a decrease in Pseudomonas counts in some patients, and symptom amelioration in most of the treated patients (12). One might criticize the study for its small size and for the fact that only patients with Pseudomonas ear infection susceptible to the applied phage were enrolled, but the study set a standard for a detailed combined clinical, microbiological, and statistical evaluation of phage therapy approaches.

The three senior authors of the mBio article (1) are members of PhageWorks, a phage solution company recently founded in Cork, Ireland, by scientists working in two important research organizations of the Irish government: the Teagasc Food Research Centre and the Alimentary Pharmabiotic Centre. The current study relies on years of research in the dairy field, but one hopes that the knowledge acquired in the food sector on practical aspects of phage research can eventually serve the biomedical research community and the development of therapeutic applications for phages as well. This reminds me of the words of Louis Pasteur, who wrote, “There are similarities between the diseases of animals and humans and the diseases of beer and wine.” For the Cork researchers, he might have spoken of “cheese and yogurt.” Looking beyond the fences of one’s “own professional specialization” can lead to important cross-fertilization.

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ACKNOWLEDGMENTS

The author is a senior research scientist at the Nestlé Research Center in Lausanne, Switzerland, and one of his research projects is on phage therapy of bacterial diarrhea.

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Footnotes

• Citation Brüssow H. 2012. Pseudomonas biofilms, cystic fibrosis, and phage: a silver lining? mBio 3(2):e00061-12. doi:10.1128/mBio.00061-12.

• Copyright © 2012 Brüssow

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

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