KJW said:

According to the Wikipedia article titled Phage Therapy

“When bacteria develop immunity to phages they generally have to give up their antibiotic resistance, always leaving a weakness that allows us to treat against them.”

Why is that?

This quote appears in wikipedia without source, so perhaps deserves a “citation needed” tag.

From KJW’s link.

“Bacteriophages are much more specific than antibiotics. They are typically harmless not only to the host organism, but also to other beneficial bacteria.”

But “a phage will only kill a bacterium if it is a match to the specific strain”. Being so specific, the target bacteria will quickly develop a resistance to them. “Early uses of phage therapy were often unreliable”.

“The discovery of bacteriophages was reported by the Englishman Frederick Twort in 1915 and the French-Canadian Felix d’Hérelle in 1917. D’Hérelle said that the phages always appeared in the stools of Shigella dysentery patients shortly before they began to recover. He “quickly learned that bacteriophages are found wherever bacteria thrive: in sewers, …”

“Actual proof for the efficacy of these phage approaches in the field or the hospital is not available”. That’s a pity.

—

From elsewhere on the web.

Phages can mediate the incorporation of genetic material into a bacteria’s genome, facilitating rapid bacterial evolution.

KJWs question leads to the more general question: “exactly how does antibiotic resistance work”? And there are a lot of different mechanisms by which it can work. Miss m knows more about this than I do. Answers can include drug inactivation, modification of cellular receptors on the membrane. I’ve noticed lice becoming resistant to treatment by increasing the length of their breeding cycle, and rabbits spending more time underground to avoid catching calicivirus.

This paper
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072922/
does not say that infection with phages causes bacteria to give up antibiotic resistance.

It also gives the warnings:

“The mechanism that caused the spread of antibiotic resistance genes between bacteria occurs most often by the gene transfer process of plasmid mediated conjugation and sometimes by phage-mediated transduction.”

“Scientific methodologies could be developed to deal with antibiotic resistance in bacteria using bacteriophage, however viral proteins would also integrate into human and animal society with unknown effect.”

A different paper says “Unfortunately, domesticated bacteria used in industrial applications are often susceptible to phage
attack”.

I haven’t read the following papers yet, but they are relevant.

Bacteriophages: an appraisal of their role in the treatment of bacterial infections
GW Hanlon – International journal of antimicrobial agents, 2007
https://sci-hub.tw/https://www.sciencedirect.com/science/article/pii/S0924857907002038

Phage therapy: past history and future prospects

—

Let’s suppose that KJW’s quote from wikipedia is correct. Then two possible mechanisms immediately occur to me.
1. Phages weaken bacteria enough for them to be susceptible to antibiotic attack, in much the same way that diseases weaken humans enough to make them susceptible to secondary infections.
2. Phages cause bacterial mutations, only a small percentage of which will retain the combination of genes necessary for antibiotic resistance.

Thanks mollwollfumble. :-)

One thing that I found interesting about phage therapy is that it’s older than antibiotics, having been developed in the Soviet Bloc separately from the west.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278648/

Because I hadn’t heard of this. That paper explains.

There seems to be some interest in the journals. But you have to check each journal to assess how good the research is too. Google Scholar search for phage therapy for papers published “since 2017”.

https://scholar.google.com.au/scholar?as_ylo=2017&q=phage+therapy&hl=en&as_sdt=0,5

At least I’d heard of bacteriopages. Not that I knew anything much.

One possibility that looks potentially promising is that, from Wikipedia,

“Phages tend to be more successful than antibiotics where there is a biofilm covered by a polysaccharide layer, which antibiotics typically cannot penetrate”.

If something could be made to eat those polysaccharides, opening the way for antibiotics to attack. Not necessarily phages.

https://web.archive.org/web/20090228204258/http://www.labnews.co.uk/printer_friendly.php/2912/combating-bacterial-infection

“Bacteria infect a surface through biofilm formation. In this case bacteria adhere to the substrate/surface. Other bacteria will adhere to the first bacteria thereby forming a coating. The adhesion process changes the characteristics of the bacteria, which will form an external polysaccharide coating. It is this polysaccharide coating which gives bacteria its resistant properties. A rapid growth and mutation rate in the bacterial genome allows it to change this polysaccharide coating and thereby adapt itself rapidly to antibiotics. Previous technologies and antibiotic therapies have focused on how to break through this polysaccharide coating.”

From another web source.

“Bacterial polysaccharides represent a diverse range of macromolecules that include peptidoglycan, lipopolysaccharides, capsules and exopolysaccharides; compounds whose functions range from structural cell-wall components (eg peptidoglycan), and important virulence factors (eg Poly-N-acetylglucosamine in S. aureus), to permitting the bacterium to survive in harsh environments (eg Pseudomonas aeruginosa in the human lung). Polysaccharide biosynthesis is a tightly regulated, energy intensive process and understanding the subtle interplay between the regulation and energy conservation, polymer modification and synthesis, and the external ecological functions is a huge area of research. The potential benefits are enormous.”

If phages can break through this polysaccharide layer …

roughbarked said:

At least I’d heard of bacteriopages. Not that I knew anything much.

Well yes, of course. But calling them phages….just means eater. And using for therapy, also seems to have some risks attached.

KJW said:

Thanks mollwollfumble. :-)

One thing that I found interesting about phage therapy is that it’s older than antibiotics, having been developed in the Soviet Bloc separately from the west.

Biological control of pests (insects, plants, bacteria) seems to have a longer history than chemical control of pests (insecticide, herbicide, antibiotic). Chemical control is more effective, but where it fails people are turning back to biological control.

From Phage therapy: past history and future prospects

Problem 4. Rapid clearance of phages
Phages were rapidly cleared by the spleen, liver and other filtering organs.
eg. Only 0.001% of injected phages still in circulation after 18 hours.

The solution.
The wild-type preparation is injected into an animal, and then blood samples are taken at progressively longer time points. Any phages found in the blood sample are reinjected. For coliphage lambda, this method increased that 0.001% to 62.5% of injected phages still in circulation after 18 hours.

In animals, phage therapy has been successful in saving animals from fatal infections of E. coli, S. typhimurium and Pseudomonas aeruginosa. There’s also been some success against Staphylococcus aureus and Klebsiella pneumoniae. A Polish group now has statistics on the treatment of approximately 1,300 cases. The overall cure rate across the spectrum of pathogens and sites of infection is approximately 86%.

“Ideal candidates for co-therapy with antibiotics.
“If a given bacterium acquires resistance to a phage, that mutation is not likely to “teach” the bacterium to resist the antibiotics. Similarly, if a given bacterium acquires resistance to an antibiotic, that mutation is not likely to “teach” the bacterium to resist the phage. There are reports that bacteria tend to mutate against antibiotics once in every 10^6 divisions, while they tend to mutate against phages once in every 10^7 divisions.”

From https://sci-hub.tw/https://www.sciencedirect.com/science/article/pii/S0924857907002038

Bacteriophages may have double or single stranded DNA or double or single stranded DNA.

This bit is interesting, and unexpected.

“Matsuda
et al. have explored the potential of lysis-deficient bac-
teriophages in the treatment of mouse peritonitis. They used
a lysis-deficient E. coli bacteriophage (t amber A3 T4) with
a mutation in the gene for the production of holin. This was
a genetically engineered mutant of T4 phage only able to
infect E. coli. Hence these phages were able to infect host
cells and to replicate within but not to lyse. The bacterial cells
were thus killed but remained largely intact following infec-
tion. When used in an experimental murine peritonitis model,
treatment with lysis-deficient phages was shown to improve
survival of the animals compared with other treatment modal-
ities. In addition, these phages killed the infecting bacteria
but in a manner that significantly minimised the release of
endotoxin”.

“One of their most important phages is a highly viru-
lent, monoclonal staphylococcal bacteriophage active against
80–95% of S. aureus strains, including MRSA. This product
can be used for local and generalised infections, includ-
ing sepsis in the newborn, osteomyelitis, wound infections,
pneumonia, etc. This phage represents an ideal agent from a
regulatory standpoint in that it has been fully characterised
both biologically and genetically”.

“‘Pyophage’ is the commercial name given to a cocktail of
phages active against staphylococci, streptococci, P. aerug-
inosa, Proteus spp. and E. coli that can be used for the
treatment and prophylaxis of purulent wound infections. It
is also used in surgery (both pre and post operatively), burn
wounds, osteomyelitis, skin infections, and eye and ear infec-
tions. This phage mixture is also used in a commercial wound
dressing product called ‘PhagoBioDerm’, which is a
novel biodegradable polymer based on poly(ester amide)s
impregnated both with the phage cocktail and the antibiotic
ciprofloxacin. The dressing has been used successfully to
treat infected wounds including those containing multiply
resistant S. aureus.”

“The ubiquitous nature of bacteriophages makes it reason-
able to suggest that fungal diseases may also be curable using phages.”

“mature bacte-
rial biofilms are able to resist antibiotic concentrations up
to 1000 times greater than those tolerated by isolated bacteria.”

“some bac-
teriophages can induce the synthesis of polysaccharide
depolymerases in order to degrade the polysaccharide that comprises
the bulk of certain biofilm matrices … So long as the phage is compatible
with the polysaccharide … dual species biofilms were not able to be similarly
eradicated.”

“Bacteriophage lysins are enzymes produced during the
infection process that specifically target bacterial peptido-
glycan and facilitate exit of viral progeny from the cell. A
number of groups have advocated the use of purified lysins
as a therapeutic tool rather than infective phage. They
have advantages over antibiotics in that they possess the host
specificity of phages”.

i wonder if you could breed something that attacks meningitis

what about if someone had some weird and wonderful infection, you take a sample , breed something specifically to kill it and then inject it

you could use this for colds perhaps, you take a mouth swab and then bred something over 48 hours to kill it

wookiemeister said:

i wonder if you could breed something that attacks meningitis

what about if someone had some weird and wonderful infection, you take a sample , breed something specifically to kill it and then inject it

Not colds, because they’re viruses. But bacterial meningitis, I think it was mentioned in one of the references.

wookiemeister said:

i wonder if you could breed something that attacks meningitis

what about if someone had some weird and wonderful infection, you take a sample , breed something specifically to kill it and then inject it

Not colds, because they’re viruses. But bacterial meningitis, I think it was mentioned in one of the references.

Yes. Here’s one.

Use of lytic bacteriophage for control of experimental Escherichia coli septicemia and meningitis in chickens and calves
P Barrow, M Lovell, A Berchieri – Clinical and Diagnostic …, 1998 – Am Soc Microbiol
http://cvi.asm.org/content/5/3/294.full.pdf

i was wondering today if you could draw the blood from the victim and pass it into a wide plate, the blood is inspected by a camera and where something odd is seen by the brain it activates a pixel over the offending blood cell / bacteria or travelling virus which blasts it with UV – killing it. if someone is very sick you inspect the blood and don’t allow infection to spread via the blood?

i was wondering today if you could draw the blood from the victim and pass it into a wide plate, the blood is inspected by a camera and where something odd is seen by the brain it activates a pixel over the offending blood cell / bacteria or travelling virus which blasts it with UV – killing it. if someone is very sick you inspect the blood and don’t allow infection to spread via the blood?

i thought colds could also be bacteria – guess i’m wrong

you then spin the blood to allow the shrivelled remains of dead virus/ bacteria / infected blood cells pass through a mesh

> what about if someone had some weird and wonderful infection, you take a sample , breed something specifically to kill it and then inject it

Breeding up takes time. If the infection is deadly it may be too late.

wookiemeister said:

i was wondering today if you could draw the blood from the victim and pass it into a wide plate, the blood is inspected by a camera and where something odd is seen by the brain it activates a pixel over the offending blood cell / bacteria or travelling virus which blasts it with UV – killing it. if someone is very sick you inspect the blood and don’t allow infection to spread via the blood?

That’s a startling idea. I don’t know if it would work but it’s offbeat enough to run it through a feasibility study. Then if it passed that through a research project.

Laminar flow through a wide thin rectangular channel. Channel thickness 12 to 15 microns. Flow rate can be a lot smaller than 5 litres per minute. As small as 5 litres per day.

Might work best for Leukaemia.

That would tell how many pixels there would need to be, and how fast the mirror would have to be for the UV laser. That in turn would determine the rate at which infection can be blasted.

Ideally LED rather than laser. That would act by heat rather than UV, which may not be ideal in the presence of platelets.

mollwollfumble said:

wookiemeister said:

i was wondering today if you could draw the blood from the victim and pass it into a wide plate, the blood is inspected by a camera and where something odd is seen by the brain it activates a pixel over the offending blood cell / bacteria or travelling virus which blasts it with UV – killing it. if someone is very sick you inspect the blood and don’t allow infection to spread via the blood?

That’s a startling idea. I don’t know if it would work but it’s offbeat enough to run it through a feasibility study. Then if it passed that through a research project.

Laminar flow through a wide thin rectangular channel. Channel thickness 12 to 15 microns. Flow rate can be a lot smaller than 5 litres per minute. As small as 5 litres per day.

Might work best for Leukaemia.

That would tell how many pixels there would need to be, and how fast the mirror would have to be for the UV laser. That in turn would determine the rate at which infection can be blasted.

Ideally LED rather than laser. That would act by heat rather than UV, which may not be ideal in the presence of platelets.

Leukemia is a disorder of bone marrow, you’d do fuck all treating the blood.

poikilotherm said:

mollwollfumble said:

wookiemeister said:

i was wondering today if you could draw the blood from the victim and pass it into a wide plate, the blood is inspected by a camera and where something odd is seen by the brain it activates a pixel over the offending blood cell / bacteria or travelling virus which blasts it with UV – killing it. if someone is very sick you inspect the blood and don’t allow infection to spread via the blood?

That’s a startling idea. I don’t know if it would work but it’s offbeat enough to run it through a feasibility study. Then if it passed that through a research project.

Laminar flow through a wide thin rectangular channel. Channel thickness 12 to 15 microns. Flow rate can be a lot smaller than 5 litres per minute. As small as 5 litres per day.

Might work best for Leukaemia.

That would tell how many pixels there would need to be, and how fast the mirror would have to be for the UV laser. That in turn would determine the rate at which infection can be blasted.

Ideally LED rather than laser. That would act by heat rather than UV, which may not be ideal in the presence of platelets.

Leukemia is a disorder of bone marrow, you’d do fuck all treating the blood.

Oops. Metastasis then.

mollwollfumble said:

poikilotherm said:

mollwollfumble said:

That’s a startling idea. I don’t know if it would work but it’s offbeat enough to run it through a feasibility study. Then if it passed that through a research project.

Laminar flow through a wide thin rectangular channel. Channel thickness 12 to 15 microns. Flow rate can be a lot smaller than 5 litres per minute. As small as 5 litres per day.

Might work best for Leukaemia.

That would tell how many pixels there would need to be, and how fast the mirror would have to be for the UV laser. That in turn would determine the rate at which infection can be blasted.

Ideally LED rather than laser. That would act by heat rather than UV, which may not be ideal in the presence of platelets.

Leukemia is a disorder of bone marrow, you’d do fuck all treating the blood.

Oops. Metastasis then.

Lymph, you’re still rooned.

poikilotherm said:

mollwollfumble said:

poikilotherm said:

Leukemia is a disorder of bone marrow, you’d do fuck all treating the blood.

Oops. Metastasis then.

Lymph, you’re still rooned.

Dang. Sickle cell anaemia?

mollwollfumble said:

wookiemeister said:

i was wondering today if you could draw the blood from the victim and pass it into a wide plate, the blood is inspected by a camera and where something odd is seen by the brain it activates a pixel over the offending blood cell / bacteria or travelling virus which blasts it with UV – killing it. if someone is very sick you inspect the blood and don’t allow infection to spread via the blood?

That’s a startling idea. I don’t know if it would work but it’s offbeat enough to run it through a feasibility study. Then if it passed that through a research project.

Laminar flow through a wide thin rectangular channel. Channel thickness 12 to 15 microns. Flow rate can be a lot smaller than 5 litres per minute. As small as 5 litres per day.

Might work best for Leukaemia.

That would tell how many pixels there would need to be, and how fast the mirror would have to be for the UV laser. That in turn would determine the rate at which infection can be blasted.

Ideally LED rather than laser. That would act by heat rather than UV, which may not be ideal in the presence of platelets.

the idea is no laser

the thin plate has small led pixels that activate and direct narrow beam of UV

the leds are small and activate when the bacteria / virus or suspect blood cell is directly above them OR

you have lines of leds and a clear plate, the camera sees the problem cell and waits for it to cross the line of death

its not perfect but if a patient had contracted something and the problem hadn’t yet been identified the blood zapper would buy time until the team understood what they were facing.

the camera watches the problem cell approach the line of UV leds and they are activated as it passes through a sandwich of leds

the bug gets zapped from above and below

wookiemeister said:

mollwollfumble said:

wookiemeister said:

i was wondering today if you could draw the blood from the victim and pass it into a wide plate, the blood is inspected by a camera and where something odd is seen by the brain it activates a pixel over the offending blood cell / bacteria or travelling virus which blasts it with UV – killing it. if someone is very sick you inspect the blood and don’t allow infection to spread via the blood?

That’s a startling idea. I don’t know if it would work but it’s offbeat enough to run it through a feasibility study. Then if it passed that through a research project.

Laminar flow through a wide thin rectangular channel. Channel thickness 12 to 15 microns. Flow rate can be a lot smaller than 5 litres per minute. As small as 5 litres per day.

Might work best for Leukaemia.

That would tell how many pixels there would need to be, and how fast the mirror would have to be for the UV laser. That in turn would determine the rate at which infection can be blasted.

Ideally LED rather than laser. That would act by heat rather than UV, which may not be ideal in the presence of platelets.

the idea is no laser

the thin plate has small led pixels that activate and direct narrow beam of UV

the leds are small and activate when the bacteria / virus or suspect blood cell is directly above them OR

you have lines of leds and a clear plate, the camera sees the problem cell and waits for it to cross the line of death

> you have lines of leds and a clear plate, the camera sees the problem cell and waits for it to cross the line of death

This one. Laminar flow connects the camera line to the line of death.

KJW said:

Thanks mollwollfumble. :-)

One thing that I found interesting about phage therapy is that it’s older than antibiotics, having been developed in the Soviet Bloc separately from the west.

They didn’t have access to Western antibiotics development so had to develop something else

Cymek said:

KJW said:

Thanks mollwollfumble. :-)

One thing that I found interesting about phage therapy is that it’s older than antibiotics, having been developed in the Soviet Bloc separately from the west.

They didn’t have access to Western antibiotics development so had to develop something else

I was thinking that, but then I remembered Lysenko.